rs149793143
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_201596.3(CACNB2):c.1180G>A(p.Val394Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,402 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V394L) has been classified as Uncertain significance.
Frequency
Consequence
NM_201596.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1180G>A | p.Val394Ile | missense_variant | 11/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1018G>A | p.Val340Ile | missense_variant | 10/13 | ENST00000377329.10 | |
LOC124902387 | XR_007062077.1 | n.596C>T | non_coding_transcript_exon_variant | 1/2 | |||
LOC124902386 | XR_007062076.1 | n.83+4993C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1180G>A | p.Val394Ile | missense_variant | 11/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1018G>A | p.Val340Ile | missense_variant | 10/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.482+4993C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251360Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135864
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461302Hom.: 0 Cov.: 30 AF XY: 0.0000550 AC XY: 40AN XY: 726992
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74292
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 23, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband; ClinVar: 1 VUS - |
Brugada syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces valine with isoleucine at codon 340 of the CACNB2 protein (p.Val340Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs149793143, ExAC 0.003%). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 22840528). ClinVar contains an entry for this variant (Variation ID: 161214). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2022 | The p.V340I variant (also known as c.1018G>A), located in coding exon 10 of the CACNB2 gene, results from a G to A substitution at nucleotide position 1018. The valine at codon 340 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at