ClinVar Genomic variation as it relates to human health
NM_000350.3(ABCA4):c.4538A>G (p.Gln1513Arg)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000350.3(ABCA4):c.4538A>G (p.Gln1513Arg)
Variation ID: 99293 Accession: VCV000099293.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p22.1 1: 94029446 (GRCh38) [ NCBI UCSC ] 1: 94495002 (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 Aug 4, 2024 Dec 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000350.3:c.4538A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000341.2:p.Gln1513Arg missense NM_001425324.1:c.4316A>G NP_001412253.1:p.Gln1439Arg missense NC_000001.11:g.94029446T>C NC_000001.10:g.94495002T>C NG_009073.1:g.96704A>G NG_009073.2:g.96702A>G P78363:p.Gln1513Arg - Protein change
- Q1513R, Q1439R
- Other names
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- Canonical SPDI
- NC_000001.11:94029445:T:C
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00005
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
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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
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 |
3743 | 4097 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Dec 11, 2023 | RCV000085646.42 | |
Likely pathogenic (2) |
criteria provided, single submitter
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Nov 16, 2018 | RCV000505160.11 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 8, 2021 | RCV001376334.9 |
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
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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
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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 pathogenic
(Nov 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001241136.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Dec 11, 2023)
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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: SCV001388934.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1513 of the ABCA4 protein (p.Gln1513Arg). … (more)
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1513 of the ABCA4 protein (p.Gln1513Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinal disease (PMID: 28559085, 29925512; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99293). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 01, 2018)
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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: SCV001248241.24
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573444.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The ABCA4 c.4538A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The ABCA4 c.4538A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PM3, PS3. Based on this evidence we have classified this variant as Likely Pathogenic. (less)
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Likely pathogenic
(Jan 01, 2015)
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no assertion criteria provided
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
unknown
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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598980.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: South East Asian
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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:
unknown
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Retina International
Accession: SCV000117785.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_ABCR:c.4538A>G
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Uncertain significance
(Dec 17, 2013)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000202090.7
First in ClinVar: Feb 02, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8. | Fujinami K | The British journal of ophthalmology | 2019 | PMID: 29925512 |
ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease. | Sangermano R | Genome research | 2018 | PMID: 29162642 |
Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease. | Stone EM | Ophthalmology | 2017 | PMID: 28559085 |
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. | Carss KJ | American journal of human genetics | 2017 | PMID: 28041643 |
Identification of three ABCA4 sequence variations exclusive to African American patients in a cohort of patients with Stargardt disease. | Utz VM | American journal of ophthalmology | 2013 | PMID: 24011517 |
ABCA4 gene screening by next-generation sequencing in a British cohort. | Fujinami K | Investigative ophthalmology & visual science | 2013 | PMID: 23982839 |
An analysis of allelic variation in the ABCA4 gene. | Webster AR | Investigative ophthalmology & visual science | 2001 | PMID: 11328725 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCA4 | - | - | - | - |
Text-mined citations for rs281865402 ...
HelpRecord last updated Sep 08, 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.