ClinVar Genomic variation as it relates to human health
NM_145200.5(CABP4):c.370C>T (p.Arg124Cys)
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.
Likely pathogenic(1); Uncertain significance(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_145200.5(CABP4):c.370C>T (p.Arg124Cys)
Variation ID: 1953 Accession: VCV000001953.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.2 11: 67456191 (GRCh38) [ NCBI UCSC ] 11: 67223662 (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 May 24, 2015 Feb 20, 2024 Dec 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_145200.5:c.370C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_660201.1:p.Arg124Cys missense NM_001300895.3:c.55C>T NP_001287824.1:p.Arg19Cys missense NM_001300896.3:c.55C>T NP_001287825.1:p.Arg19Cys missense NM_001379183.1:c.55C>T NP_001366112.1:p.Arg19Cys missense NC_000011.10:g.67456191C>T NC_000011.9:g.67223662C>T NG_021211.1:g.5845C>T P57796:p.Arg124Cys - Protein change
- R124C, R19C
- Other names
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- Canonical SPDI
- NC_000011.10:67456190:C: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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0.00040 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00016
The Genome Aggregation Database (gnomAD), exomes 0.00018
Trans-Omics for Precision Medicine (TOPMed) 0.00020
The Genome Aggregation Database (gnomAD) 0.00022
1000 Genomes Project 30x 0.00031
1000 Genomes Project 0.00040
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
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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
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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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CABP4 | - | - |
GRCh38 GRCh37 |
380 | 407 |
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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Uncertain significance (2) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000002030.7 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Dec 28, 2023 | RCV001049798.7 |
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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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cone-rod synaptic disorder, congenital nonprogressive
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001260991.1
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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Nov 30, 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: SCV002072824.2
First in ClinVar: Feb 04, 2022 Last updated: Dec 17, 2022 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23099293, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23099293, 31589614, 33369259, 34426522, 16960802, 35791102) (less)
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Likely pathogenic
(Dec 28, 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: SCV001213869.4
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 124 of the CABP4 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 124 of the CABP4 protein (p.Arg124Cys). This variant is present in population databases (rs121917828, gnomAD 0.05%). This missense change has been observed in individual(s) with congenital stationary night blindness (PMID: 16960802). 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: 1953). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CABP4 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(Oct 01, 2006)
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no assertion criteria provided
Method: literature only
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CONE-ROD SYNAPTIC DISORDER, CONGENITAL NONPROGRESSIVE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022188.2
First in ClinVar: Apr 04, 2013 Last updated: May 24, 2015 |
Comment on evidence:
In a 15-year-old boy of Swiss ancestry with congenital nonprogressive cone-rod synaptic disorder (CRSD; 610427), Zeitz et al. (2006) identified compound heterozygosity for a 2-bp … (more)
In a 15-year-old boy of Swiss ancestry with congenital nonprogressive cone-rod synaptic disorder (CRSD; 610427), Zeitz et al. (2006) identified compound heterozygosity for a 2-bp deletion in the CABP4 gene (608965.0001) and a c.370C-T transition in exon 2, predicted to introduce a binding site for SRp55 (SRSF6; 601944) and influence splicing, or to result in an arg124-to-cys (R124C) substitution. His unaffected parents were each heterozygous for 1 of the mutations, which were not found in 216 or 228 control alleles, respectively. The patient exhibited CABP4 transcript levels 30 to 40% of those found in controls. (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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Structural insights into activation of the retinal L-type Ca²⁺ channel (Cav1.4) by Ca²⁺-binding protein 4 (CaBP4). | Park S | The Journal of biological chemistry | 2014 | PMID: 25258313 |
Clinical characterisation of the CABP4-related retinal phenotype. | Khan AO | The British journal of ophthalmology | 2013 | PMID: 23099293 |
A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype. | Aldahmesh MA | Molecular vision | 2010 | PMID: 20157620 |
A novel homozygous nonsense mutation in CABP4 causes congenital cone-rod synaptic disorder. | Littink KW | Investigative ophthalmology & visual science | 2009 | PMID: 19074807 |
Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness. | Zeitz C | American journal of human genetics | 2006 | PMID: 16960802 |
Text-mined citations for rs121917828 ...
HelpRecord last updated Feb 28, 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.