VCV000852740.8 - ClinVar - NCBI (2024)

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.

Identifiers

NM_001297.5(CNGB1):c.3286G>A (p.Val1096Met)

Variation ID: 852740 Accession: VCV000852740.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q21 16: 57888031 (GRCh38) [ NCBI UCSC ] 16: 57921935 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Apr 15, 2020	May 1, 2024	Oct 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001297.5:c.3286G>A MANESelect Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001288.3:p.Val1096Met	missense
NM_001286130.2:c.3268G>A	NP_001273059.1:p.Val1090Met	missense
NC_000016.10:g.57888031C>T
NC_000016.9:g.57921935C>T
NG_016351.1:g.88086G>A

... more HGVS ... less HGVS

Protein change

V1096M, V1090M

Other names

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Canonical SPDI

NC_000016.10:57888030:C:T

Functional
consequence Help

The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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Global minor allele
frequency (GMAF) Help

The 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) 0.00019

Trans-Omics for Precision Medicine (TOPMed) 0.00019

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00024

Links

dbSNP: rs376128303

VarSome

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1096 of the CNGB1 protein (p.Val1096Met). This variant is present in population databases (rs376128303, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNGB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 852740). 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 not expected to disrupt CNGB1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The c.3286G>A (p.V1096M) alteration is located in exon 32 (coding exon 31) of the CNGB1 gene. This alteration results from a G to A substitution at nucleotide position 3286, causing the valine (V) at amino acid position 1096 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.