10-18192151-A-G

Position:

• chr10-18192151-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):​c.213+41176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 151,660 control chromosomes in the GnomAD database, including 50,453 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50453 hom., cov: 29)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

Genes affected

CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.213+41176A>G		intron_variant		ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.213+41176A>G		intron_variant		1	NM_201596.3	ENSP00000320025

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123490 AN: 151542 Hom.: 50421 Cov.: 29

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.815 AC: 123577 AN: 151660 Hom.: 50453 Cov.: 29 AF XY: 0.816 AC XY: 60419 AN XY: 74026

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.825

Alfa AF: 0.837 Hom.: 73552

Bravo AF: 0.811

Asia WGS AF: 0.789 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2482100; hg19: chr10-18481080;