ClinVar Genomic variation as it relates to human health
NM_201253.3(CRB1):c.2401A>T (p.Lys801Ter)
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.2401A>T (p.Lys801Ter)
Variation ID: 5736 Accession: VCV000005736.55
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q31.3 1: 197427726 (GRCh38) [ NCBI UCSC ] 1: 197396856 (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 13, 2018 Oct 8, 2024 Mar 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_201253.3:c.2401A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_957705.1:p.Lys801Ter nonsense NM_001193640.2:c.2065A>T NP_001180569.1:p.Lys689Ter nonsense NM_001257965.2:c.2194A>T NP_001244894.1:p.Lys732Ter nonsense NM_001257966.2:c.2128+5770A>T intron variant NR_047563.2:n.2354A>T non-coding transcript variant NR_047564.2:n.2562A>T non-coding transcript variant NC_000001.11:g.197427726A>T NC_000001.10:g.197396856A>T NG_008483.2:g.231265A>T - Protein change
- K801*, K732*, K689*
- Other names
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- Canonical SPDI
- NC_000001.11:197427725:A:T
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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.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00009
The Genome Aggregation Database (gnomAD) 0.00013
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
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 |
1941 | 1966 |
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
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 (2) |
criteria provided, single submitter
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Apr 11, 2023 | RCV000006090.7 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 9, 2022 | RCV000578757.41 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2024 | RCV000691427.9 | |
Pathogenic (1) |
no assertion criteria provided
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Apr 1, 2018 | RCV000787578.2 | |
Pathogenic (2) |
criteria provided, single submitter
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May 8, 2019 | RCV000787826.4 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 9, 2024 | RCV001250606.6 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001275651.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 11, 2023 | RCV003450616.1 | |
CRB1-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Sep 10, 2024 | RCV004739293.1 |
Pathogenic (1) |
criteria provided, single submitter
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Sep 22, 2021 | RCV002504753.3 |
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
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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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Pathogenic
(Nov 14, 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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Eurofins Ntd Llc (ga)
Accession: SCV000232367.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Apr 24, 2018)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000883683.1
First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018 |
Comment:
The CRB1 c.2401A>T; p.Lys801Ter variant (rs137853137) is reported in the medical literature in several individuals with a clinical diagnosis of autosomal recessive retinitis pigmentosa, with … (more)
The CRB1 c.2401A>T; p.Lys801Ter variant (rs137853137) is reported in the medical literature in several individuals with a clinical diagnosis of autosomal recessive retinitis pigmentosa, with the majority of individuals carrying an additional pathogenic CRB1 variant (den Hollander 2001, Henderson 2011, Strom 2012) and has been implicated as a common pathogenic CRB1 variant (Coppieters 2010). The variant is listed as pathogenic in the ClinVar database by several sources (Variation ID: 5736). This variant is found in the general population with an overall allele frequency of 0.006% (16/276488 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Coppieters F et al. Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. Hum Mutat. 2010 Oct;31(10):E1709-66. den Hollander AI et al. Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum Genet. 2001 Jul;69(1):198-203. Henderson RH et al. Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1. Br J Ophthalmol. 2011 Jun;95(6):811-7. Strom SP et al. Molecular diagnosis of putative Stargardt Disease probands by exome sequencing. BMC Med Genet. 2012 Aug 3;13:67. (less)
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Pathogenic
(May 08, 2019)
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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: SCV001240329.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Dec 09, 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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GeneDx
Accession: SCV000680516.4
First in ClinVar: Feb 13, 2018 Last updated: Dec 24, 2022 |
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: 32531858, 34003923, 30718709, 22863181, 24265693, 25525159, 11389483, 20956273, 28559085, 33387055, 31589614, 32037395, 34884448) (less)
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Pathogenic
(Sep 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Pigmented paravenous retinochoroidal atrophy
Retinitis pigmentosa 12 Leber congenital amaurosis 8
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002815060.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 09, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000819205.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys801*) 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.Lys801*) 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 (rs137853137, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis, early-onset rod-cone dystrophy, or autosomal recessive retinitis pigmentosa (PMID: 11389483, 20956273, 24265693). ClinVar contains an entry for this variant (Variation ID: 5736). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 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: SCV001248713.25
First in ClinVar: May 12, 2020 Last updated: Oct 08, 2024 |
Number of individuals with the variant: 3
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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: SCV004180043.1
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: SCV004180044.1
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: SCV004180045.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Oct 17, 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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Revvity Omics, Revvity
Accession: SCV002019728.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 09, 2024)
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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: SCV004211114.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jul 01, 2001)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 12
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026272.3
First in ClinVar: Apr 04, 2013 Last updated: Dec 01, 2018 |
Comment on evidence:
In a brother and sister with retinitis pigmentosa (RP12; 600105) who developed a Coats-like exudative vasculopathy (see 300216), den Hollander et al. (2001) found compound … (more)
In a brother and sister with retinitis pigmentosa (RP12; 600105) who developed a Coats-like exudative vasculopathy (see 300216), den Hollander et al. (2001) found compound heterozygosity for a nonsense mutation, lys801 to ter (K801X), and a missense mutation, cys1181 to arg (C1181R; 604210.0009), in the CRB1 gene. (less)
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Pathogenic
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926558.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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Pathogenic
(Apr 01, 2018)
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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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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926839.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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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: SCV001425474.1
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: SCV001460942.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Sep 10, 2024)
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no assertion criteria provided
Method: clinical testing
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CRB1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005360360.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The CRB1 c.2401A>T variant is predicted to result in premature protein termination (p.Lys801*). This variant has been reported in the homozygous and compound heterozygous states … (more)
The CRB1 c.2401A>T variant is predicted to result in premature protein termination (p.Lys801*). This variant has been reported in the homozygous and compound heterozygous states in individuals with with Leber congenital amaurosis or early-onset retinal disease (den Hollander et al. 2001. PubMed ID: 11389483; Henderson et al. 2010. PubMed ID: 20956273; Eisenberger et al. 2013. PubMed ID: 24265693). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in CRB1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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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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Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
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 |
Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies. | Eisenberger T | PloS one | 2013 | PMID: 24265693 |
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 |
Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. | den Hollander AI | American journal of human genetics | 2001 | PMID: 11389483 |
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 rs137853137 ...
HelpRecord last updated Oct 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.