rs12356676

chr10-18358575-A-Gchr10-18358575-A-T

Variant summary

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

The NM_201596.3(CACNB2):c.214-43349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 141,010 control chromosomes in the GnomAD database, including 34,136 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 0.70 (34136 hom., cov: 23)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-1.12).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.51+17598A>G		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.214-43349A>G		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-43349A>G		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.51+17598A>G		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 98391 AN: 140922 Hom.: 34127 Cov.: 23

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.698 AC: 98434 AN: 141010 Hom.: 34136 Cov.: 23 AF XY: 0.699 AC XY: 47573 AN XY: 68072

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.680

Alfa AF: 0.688 Hom.: 4162

Bravo AF: 0.664

Asia WGS AF: 0.495 AC: 1643 AN: 3316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	2.7
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12356676; hg19: chr10-18647504;