ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.1418del (p.Gly473fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.1418del (p.Gly473fs)
Variation ID: 53251 Accession: VCV000053251.22
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117559487 (GRCh38) [ NCBI UCSC ] 7: 117199541 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 23, 2015 May 1, 2024 Mar 17, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.1418del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Gly473fs frameshift NM_000492.3:c.1418delG NC_000007.14:g.117559489del NC_000007.13:g.117199543del NG_016465.4:g.98706del LRG_663:g.98706del - Protein change
- Other names
- 1548delG
- Canonical SPDI
- NC_000007.14:117559486:GGG:GG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3704 | 5025 | |
CFTR-AS1 | - | - | - | GRCh38 | - | 490 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (8) |
reviewed by expert panel
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Mar 17, 2017 | RCV000046300.15 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 29, 2022 | RCV000507504.11 | |
CFTR-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Mar 17, 2017 | RCV001831727.1 |
Pathogenic (1) |
criteria provided, single submitter
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Oct 11, 2023 | RCV003473454.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Mar 17, 2017)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Study: CFTR2
Accession: SCV000245878.2 First in ClinVar: Sep 23, 2015 Last updated: Dec 12, 2017 |
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Pathogenic
(Jan 29, 2018)
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criteria provided, single submitter
Method: curation
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cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR-France
Accession: SCV001169482.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
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Pathogenic
(Apr 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601044.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022 |
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Pathogenic
(Mar 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502392.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Apr 05, 2016)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486133.2
First in ClinVar: Sep 23, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004213318.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jul 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019243.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001587420.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly473Glufs*54) in the CFTR gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gly473Glufs*54) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 9429141, 21198395, 23974870, 26708955, 26905352). This variant is also known as 1548delG. ClinVar contains an entry for this variant (Variation ID: 53251). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848805.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The c.1418delG (p.Gly473Glufs*54) variant in CFTR (also known as c.1548delG) has been reported in at least 12 individuals with cystic fibrosis from 10 Saudi families, … (more)
The c.1418delG (p.Gly473Glufs*54) variant in CFTR (also known as c.1548delG) has been reported in at least 12 individuals with cystic fibrosis from 10 Saudi families, in both the homozygous state and in the heterozygous state with the p.Asn1303Lys variant (El-Harith 1997 PMID: 9429141, Banjar 1999 PMID: 11924117, Monies 1029 PMID: 31130284). It has also been identified in 0.0024% (1/41454) of African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with a recessive allele frequency. This variant has also been reported in ClinVar (Variation ID 53251). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 473 and leads to a premature termination codon 54 amino acids downstream. Loss of function of the CFTR gene is an established disease mechanism in autosomal recessive cystic fibrosis. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive cystic fibrosis. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting. (less)
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Pathogenic
(May 11, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002697298.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1418delG pathogenic mutation, located in coding exon 11 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1418, causing … (more)
The c.1418delG pathogenic mutation, located in coding exon 11 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1418, causing a translational frameshift with a predicted alternate stop codon (p.G473Efs*54). This mutation was first described in two affected individuals with pancreatic insufficiency in Saudi Arabia; one individual was compound heterozygous with a deleterious mutation, but a second alteration was not identified in the other individual (el-Harith EA et al. J. Med. Genet., 1997 Dec;34:996-9). Another study determined this was one of the most common disease-causing mutations in the Saudi Arabian population, accounting for 17% of disease alleles (Kambouris M et al. Eur. J. Pediatr., 2000 May;159:303-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Oct 27, 2016)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696843.1
First in ClinVar: Dec 12, 2017 Last updated: Dec 12, 2017 |
Comment:
Variant summary: The CFTR c.1418delG (p.Gly473Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense … (more)
Variant summary: The CFTR c.1418delG (p.Gly473Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Ser489X, p.Gln493X, p.Glu514X). One in silico tool predicts a damaging outcome for this variant. This variant is absent from 121306 control chromosomes and has been reported in numerous affected individuals in the literature, and is specifically noted as being a common disease causing mutation in the Arab population. In addition, the CFTR2 database has classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Oct 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714238.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PVS1, PM2, PP4, PP5
Number of individuals with the variant: 1
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806753.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002080593.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A genomics approach to male infertility. | Alhathal N | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32719396 |
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. | Monies D | American journal of human genetics | 2019 | PMID: 31130284 |
Sequencing as a first-line methodology for cystic fibrosis carrier screening. | Beauchamp KA | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 31036917 |
CFTR Gene Mutations in the Egyptian Population: Current and Future Insights for Genetic Screening Strategy. | El-Seedy AS | Frontiers in genetics | 2017 | PMID: 28408918 |
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations in North Egyptian population: implications for the genetic diagnosis in Egypt. | El-Seedy A | Cellular and molecular biology (Noisy-le-Grand, France) | 2016 | PMID: 28040058 |
Growth assessment and risk factors of malnutrition in children with cystic fibrosis. | Isa HM | Saudi medical journal | 2016 | PMID: 26905352 |
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. | Schrijver I | The Journal of molecular diagnostics : JMD | 2016 | PMID: 26708955 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
Spectrum of CFTR gene mutations in Iranian Azeri Turkish patients with cystic fibrosis. | Bonyadi M | Genetic testing and molecular biomarkers | 2011 | PMID: 21198395 |
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry. | Alonso MJ | Annals of human genetics | 2007 | PMID: 17331079 |
Identification of novel mutations in Arabs with cystic fibrosis and their impact on the cystic fibrosis transmembrane regulator mutation detection rate in Arab populations. | Kambouris M | European journal of pediatrics | 2000 | PMID: 10834512 |
Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia. | Banjar H | Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit | 1999 | PMID: 11924117 |
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. | Cohn JA | The New England journal of medicine | 1998 | PMID: 9725922 |
Novel and characteristic CFTR mutations in Saudi Arab children with severe cystic fibrosis. | el-Harith EA | Journal of medical genetics | 1997 | PMID: 9429141 |
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR. | Yang Y | Human molecular genetics | 1993 | PMID: 7691345 |
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. | Cutting GR | Nature | 1990 | PMID: 1695717 |
https://cftr2.org | - | - | - | - |
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Text-mined citations for rs397508205 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.