rs12240995

chr10-18348303-A-C

Variant summary

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

The NM_201596.3(CACNB2):c.214-53621A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,252 control chromosomes in the GnomAD database, including 1,185 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 0.12 (1185 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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 = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.51+7326A>C		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.214-53621A>C		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-53621A>C		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.51+7326A>C		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18180 AN: 152134 Hom.: 1179 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18219 AN: 152252 Hom.: 1185 Cov.: 32 AF XY: 0.117 AC XY: 8693 AN XY: 74450

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.0698

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.105

Alfa AF: 0.122 Hom.: 752

Bravo AF: 0.127

Asia WGS AF: 0.0660 AC: 228 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	0.90
Dann	Benign	0.61

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: rs12240995; hg19: chr10-18637232;