Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 36460718, 21911583, 20696155, 10958763, 29848554, 32619608, 23953153, 25066811, 25283059, 25525159, 26311262, 28947085, 30093795, 32845068, 29847651, 35119454, 31964843, 31725702, 32783370, 35120629)
ClinVar Genomic variation as it relates to human health
NM_000350.3(ABCA4):c.3898C>T (p.Arg1300Ter)
Germline
Classification
Help
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.
(8)
Help
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
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000350.3(ABCA4):c.3898C>T (p.Arg1300Ter)
Variation ID: 99245 Accession: VCV000099245.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p22.1 1: 94032008 (GRCh38) [ NCBI UCSC ] 1: 94497564 (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 Sep 16, 2024 May 30, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000350.3:c.3898C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000341.2:p.Arg1300Ter nonsense NM_001425324.1:c.3676C>T NP_001412253.1:p.Arg1226Ter nonsense NC_000001.11:g.94032008G>A NC_000001.10:g.94497564G>A NG_009073.1:g.94142C>T NG_009073.2:g.94140C>T - Protein change
- R1300*, R1226*
- Other names
- -
- Canonical SPDI
- NC_000001.11:94032007: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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| ABCA4 | - | - |
GRCh38 GRCh37 |
3759 | 4113 | |
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. |
|---|---|---|---|---|
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
May 30, 2024 | RCV000085598.13 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 12, 2019 | RCV001073602.2 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 23, 2021 | RCV001727570.4 |
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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|---|---|---|---|---|---|
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Pathogenic
(May 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000890193.2
First in ClinVar: Mar 19, 2019 Last updated: Sep 16, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 36460718, 21911583, 20696155, 10958763, 29848554, 32619608, 23953153, 25066811, 25283059, 25525159, 26311262, 28947085, 30093795, 32845068, 29847651, 35119454, 31964843, 31725702, 32783370, 35120629) (less)
|
|
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Pathogenic
(Jul 12, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001239153.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
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Pathogenic
(Dec 23, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019777.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Dec 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001377167.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1300*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg1300*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61752427, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with Stargardt disease (PMID: 10958763, 30093795). ClinVar contains an entry for this variant (Variation ID: 99245). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Aug 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Severe early-childhood-onset retinal dystrophy
(Autosomal recessive inheritance)
Affected status: no
Allele origin:
germline
|
Genetic Diagnostics Department, Viafet Genomics Laboratory
Accession: SCV001976442.1
First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
Comment:
As part of Carrier Screening testing performed at Viafet Genomics Laboratory, this variant was identified in a heterozygous state in a patient who is not … (more)
As part of Carrier Screening testing performed at Viafet Genomics Laboratory, this variant was identified in a heterozygous state in a patient who is not affected with this condition. This variant is present in exon 27/50 in the only transcript of this gene. Several loss-of-function variants are reported as disease-causing in HGMD and/or ClinVar after this position. Salles et al., 2018 have identified this variant in a compound heterozygous state with c.1804C>T (p.Arg602Trp) in a patient affected with Stargardt disease (PMID: 30093795). Méjécase et al., 2020 have identified this variant along with c.5882G>A (p.Gly1961Glu) and c.2570T>C (p.Leu857Pro) in a patient affected with Stargardt disease (PMID: 32783370). (less)
Number of individuals with the variant: 1
Secondary finding: yes
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV004013499.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). The variant is predicted to result in … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099245 / PMID: 10958763). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Retinal dystrophy (present) , Rod-cone dystrophy (present) , Abnormal retinal morphology (present)
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Severe early-childhood-onset retinal dystrophy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana
Accession: SCV005047008.1
First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024 |
|
|
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not provided
(-)
|
no classification provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
not provided
|
Retina International
Accession: SCV000117736.1
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.3898C>T
|
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Arg1300*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61752427, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with Stargardt disease (PMID: 10958763, 30093795). ClinVar contains an entry for this variant (Variation ID: 99245). For these reasons, this variant has been classified as Pathogenic.
Comment:
As part of Carrier Screening testing performed at Viafet Genomics Laboratory, this variant was identified in a heterozygous state in a patient who is not affected with this condition. This variant is present in exon 27/50 in the only transcript of this gene. Several loss-of-function variants are reported as disease-causing in HGMD and/or ClinVar after this position. Salles et al., 2018 have identified this variant in a compound heterozygous state with c.1804C>T (p.Arg602Trp) in a patient affected with Stargardt disease (PMID: 30093795). Méjécase et al., 2020 have identified this variant along with c.5882G>A (p.Gly1961Glu) and c.2570T>C (p.Leu857Pro) in a patient affected with Stargardt disease (PMID: 32783370).
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099245 / PMID: 10958763). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
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. |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 36460718, 21911583, 20696155, 10958763, 29848554, 32619608, 23953153, 25066811, 25283059, 25525159, 26311262, 28947085, 30093795, 32845068, 29847651, 35119454, 31964843, 31725702, 32783370, 35120629)
Comment:
This sequence change creates a premature translational stop signal (p.Arg1300*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61752427, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with Stargardt disease (PMID: 10958763, 30093795). ClinVar contains an entry for this variant (Variation ID: 99245). For these reasons, this variant has been classified as Pathogenic.
Comment:
As part of Carrier Screening testing performed at Viafet Genomics Laboratory, this variant was identified in a heterozygous state in a patient who is not affected with this condition. This variant is present in exon 27/50 in the only transcript of this gene. Several loss-of-function variants are reported as disease-causing in HGMD and/or ClinVar after this position. Salles et al., 2018 have identified this variant in a compound heterozygous state with c.1804C>T (p.Arg602Trp) in a patient affected with Stargardt disease (PMID: 30093795). Méjécase et al., 2020 have identified this variant along with c.5882G>A (p.Gly1961Glu) and c.2570T>C (p.Leu857Pro) in a patient affected with Stargardt disease (PMID: 32783370).
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099245 / PMID: 10958763). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The genetic landscape of inherited eye disorders in 74 consecutive families from the United Arab Emirates. | Méjécase C | American journal of medical genetics. Part C, Seminars in medical genetics | 2020 | PMID: 32783370 |
| Variants in the ABCA4 gene in a Brazilian population with Stargardt disease. | Salles MV | Molecular vision | 2018 | PMID: 30093795 |
| Screening of ABCA4 Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations. | Jiang F | Investigative ophthalmology & visual science | 2016 | PMID: 26780318 |
| Clinical and molecular characteristics of childhood-onset Stargardt disease. | Fujinami K | Ophthalmology | 2015 | PMID: 25312043 |
| Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing. | Xu Y | Human genetics | 2014 | PMID: 24938718 |
| The clinical effect of homozygous ABCA4 alleles in 18 patients. | Fujinami K | Ophthalmology | 2013 | PMID: 23769331 |
| A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. | Rivera A | American journal of human genetics | 2000 | PMID: 10958763 |
| Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy. | Maugeri A | American journal of human genetics | 2000 | PMID: 10958761 |
Text-mined citations for rs61752427 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.