ClinVar Genomic variation as it relates to human health
NM_000350.3(ABCA4):c.2690C>T (p.Thr897Ile)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Likely pathogenic(1); Uncertain significance(3); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000350.3(ABCA4):c.2690C>T (p.Thr897Ile)
Variation ID: 99153 Accession: VCV000099153.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p22.1 1: 94048921 (GRCh38) [ NCBI UCSC ] 1: 94514477 (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 Feb 20, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000350.3:c.2690C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000341.2:p.Thr897Ile missense NM_001425324.1:c.2468C>T NP_001412253.1:p.Thr823Ile missense NC_000001.11:g.94048921G>A NC_000001.10:g.94514477G>A NG_009073.1:g.77229C>T NG_009073.2:g.77227C>T P78363:p.Thr897Ile - Protein change
- T897I, T823I
- Other names
- -
- Canonical SPDI
- NC_000001.11:94048920:G:A
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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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0.00160 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00108
Exome Aggregation Consortium (ExAC) 0.00114
The Genome Aggregation Database (gnomAD), exomes 0.00122
1000 Genomes Project 0.00160
Trans-Omics for Precision Medicine (TOPMed) 0.00123
The Genome Aggregation Database (gnomAD) 0.00133
1000 Genomes Project 30x 0.00156
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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ABCA4 | - | - |
GRCh38 GRCh37 |
3701 | 4056 |
Conditions - Germline
Condition
Help
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
Help
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
Help
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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Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000085500.33 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000260644.6 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000280747.6 | |
Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000315748.6 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000375069.6 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2016 | RCV000408596.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 11, 2018 | RCV001197697.3 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001096530.5 |
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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Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Cone-Rod Dystrophy, Recessive
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000359446.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
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Retinitis Pigmentosa, Recessive
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000359444.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Macular Degeneration
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000359445.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Stargardt Disease, Recessive
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000359447.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV000281851.2
First in ClinVar: Dec 07, 2016 Last updated: Dec 07, 2016 |
Indication for testing: Stargardt disease 1
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Uncertain significance
(Sep 14, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000345363.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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ABCA4-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001252749.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Uncertain significance
(Oct 11, 2018)
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criteria provided, single submitter
Method: clinical testing
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Age related macular degeneration 2
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368476.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Uncertain significance. The available evidence favors the benign nature of this variant, however the evidence is insufficent to prove its … (more)
This variant was classified as: Uncertain significance. The available evidence favors the benign nature of this variant, however the evidence is insufficent to prove its benign nature. The following ACMG criteria were applied in classifying this variant: BP6. (less)
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Uncertain significance
(Apr 05, 2019)
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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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GeneDx
Accession: SCV000321346.6
First in ClinVar: Oct 09, 2016 Last updated: Dec 06, 2016 |
Comment:
Reported previously in association with Stargardt disease and cone-rod dystrophy as heterozygous with other ABCA4 variants (Salles et al., 2018) as well as heterozygous without … (more)
Reported previously in association with Stargardt disease and cone-rod dystrophy as heterozygous with other ABCA4 variants (Salles et al., 2018) as well as heterozygous without a second variant (Simonelli et al., 2000; Tsipi et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 10711710, 11328725, 22995991, 27014590, 22264887, 21911583, 26103963, 30093795, 28118664, 29178665, 11702214, 29925512, 18161617) (less)
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Likely benign
(Jan 31, 2024)
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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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Invitae
Accession: SCV001029034.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Pathogenic
(Aug 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001147338.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922726.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958534.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964173.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Retina International
Accession: SCV000117637.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014 |
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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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Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs. | Schulz HL | Investigative ophthalmology & visual science | 2017 | PMID: 28118664 |
Genomic screening of ABCA4 and array CGH analysis underline the genetic variability of Greek patients with inherited retinal diseases. | Tsipi M | Meta gene | 2016 | PMID: 27014590 |
Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation. | Boulanger-Scemama E | Orphanet journal of rare diseases | 2015 | PMID: 26103963 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy. | Thiadens AA | Ophthalmology | 2012 | PMID: 22264887 |
Analysis of the ABCA4 gene by next-generation sequencing. | Zernant J | Investigative ophthalmology & visual science | 2011 | PMID: 21911583 |
Mutational scanning of the ABCR gene with double-gradient denaturing-gradient gel electrophoresis (DG-DGGE) in Italian Stargardt disease patients. | Fumagalli A | Human genetics | 2001 | PMID: 11702214 |
An analysis of allelic variation in the ABCA4 gene. | Webster AR | Investigative ophthalmology & visual science | 2001 | PMID: 11328725 |
New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease. | Simonelli F | Investigative ophthalmology & visual science | 2000 | PMID: 10711710 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCA4 | - | - | - | - |
Text-mined citations for rs61749440 ...
HelpRecord last updated Apr 15, 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.