ClinVar Genomic variation as it relates to human health
NM_201253.3(CRB1):c.2688T>A (p.Cys896Ter)
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_201253.3(CRB1):c.2688T>A (p.Cys896Ter)
Variation ID: 99888 Accession: VCV000099888.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q31.3 1: 197429460 (GRCh38) [ NCBI UCSC ] 1: 197398590 (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 Feb 28, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_201253.3:c.2688T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_957705.1:p.Cys896Ter nonsense NM_001193640.2:c.2352T>A NP_001180569.1:p.Cys784Ter nonsense NM_001257965.2:c.2616T>A NP_001244894.1:p.Cys872Ter nonsense NM_001257966.2:c.2129-6140T>A intron variant NR_047563.2:n.2641T>A non-coding transcript variant NR_047564.2:n.2849T>A non-coding transcript variant NC_000001.11:g.197429460T>A NC_000001.10:g.197398590T>A NG_008483.2:g.232999T>A - Protein change
- C896*, C872*, C784*
- Other names
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- Canonical SPDI
- NC_000001.11:197429459:T: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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
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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CRB1 | - | - |
GRCh38 GRCh37 |
1911 | 1935 |
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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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2023 | RCV000086328.11 | |
Pathogenic (2) |
criteria provided, single submitter
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Oct 27, 2017 | RCV000505142.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000542027.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 18, 2018 | RCV001074017.2 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2023 | RCV001250608.3 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001275654.1 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV001376474.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2021 | RCV001723672.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 11, 2023 | RCV003453019.1 |
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
(Oct 27, 2017)
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criteria provided, single submitter
Method: research
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Macular dystrophy
Affected status: yes
Allele origin:
germline
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Molecular Medicine, University of Leeds
Accession: SCV000611554.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
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Pathogenic
(Oct 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 8
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211105.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 22, 2020)
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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: SCV002019727.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Oct 18, 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: SCV001239583.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Retinitis pigmentosa 12
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573628.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The CRB1 c.2688T>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The CRB1 c.2688T>A 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: PVS1, PM2, PP5. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(Apr 01, 2021)
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criteria provided, single submitter
Method: curation
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Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950250.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Cys896Ter variant in CRB1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Cys896Ter variant in CRB1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP5. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. (less)
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Pathogenic
(Jul 01, 2023)
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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: SCV000576655.4
First in ClinVar: Feb 20, 2014 Last updated: Jul 08, 2023 |
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 … (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: 15024725, 34003923, 25525159, 28041643, 29391521, 28559085, 20956273, 31875109, 32036094, 32581362, 31589614, 32037395, 35119454) (less)
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Pathogenic
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 8
Retinitis pigmentosa 12
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000650637.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys896*) in the CRB1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Cys896*) in the CRB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). This variant is present in population databases (rs62636273, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis, early-onset retinal dystrophy, and retinitis pigmentosa (PMID: 15024725, 20683928, 20956273, 23379534). ClinVar contains an entry for this variant (Variation ID: 99888). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 02, 2014)
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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: SCV000232816.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 8
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004180069.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 12
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004180072.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pigmented paravenous retinochoroidal atrophy
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004180071.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Jan 01, 2015)
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no assertion criteria provided
Method: research
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Macular dystrophy
Affected status: yes
Allele origin:
unknown
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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598917.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Observation 1:
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
Observation 2:
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Leber congenital amaurosis 8
Affected status: yes
Allele origin:
inherited
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Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001425476.1
First in ClinVar: Aug 01, 2020 Last updated: Aug 01, 2020 |
Number of individuals with the variant: 3
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Leber congenital amaurosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460945.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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: SCV000118474.1
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_CRB1:c.2688T>A
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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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The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK). | Zampaglione E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906470 |
A clinical and molecular characterisation of CRB1-associated maculopathy. | Khan KN | European journal of human genetics : EJHG | 2018 | PMID: 29391521 |
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 |
Next-generation sequencing-based comprehensive molecular analysis of 43 Japanese patients with cone and cone-rod dystrophies. | Oishi M | Molecular vision | 2016 | PMID: 26957898 |
Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing. | Consugar MB | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25412400 |
High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population. | Corton M | Orphanet journal of rare diseases | 2013 | PMID: 23379534 |
CRB1 mutations in inherited retinal dystrophies. | Bujakowska K | Human mutation | 2012 | PMID: 22065545 |
Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1. | Henderson RH | The British journal of ophthalmology | 2011 | PMID: 20956273 |
Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. | Coppieters F | Human mutation | 2010 | PMID: 20683928 |
Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. | Hanein S | Human mutation | 2004 | PMID: 15024725 |
Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). | den Hollander AI | Nature genetics | 1999 | PMID: 10508521 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CRB1 | - | - | - | - |
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Text-mined citations for rs62636273 ...
HelpRecord last updated May 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.