rs11013860

Positions:

• chr10-18365098-A-C
• chr10-18365098-A-G
• chr10-18365098-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.214-36826A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,188 control chromosomes in the GnomAD database, including 1,652 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 0.11 (1652 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201590.3	c.51+24121A>C		intron_variant		ENST00000377329.10	NP_963884.2
CACNB2	NM_201596.3	c.214-36826A>C		intron_variant		ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-36826A>C		intron_variant		1	NM_201596.3	ENSP00000320025
CACNB2	ENST00000377329.10	c.51+24121A>C		intron_variant		1	NM_201590.3	ENSP00000366546

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16923 AN: 152070 Hom.: 1648 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.111 AC: 16941 AN: 152188 Hom.: 1652 Cov.: 32 AF XY: 0.119 AC XY: 8839 AN XY: 74400

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0746 Hom.: 728

Bravo AF: 0.108

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.72

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: rs11013860; hg19: chr10-18654027;