rs10828616

chr10-18381088-G-Achr10-18381088-G-Cchr10-18381088-G-T

Variant summary

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

The NM_201596.3(CACNB2):c.214-20836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,292 control chromosomes in the GnomAD database, including 5,233 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 0.25 (5233 hom., cov: 28)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.52-20836G>A		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.214-20836G>A		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-20836G>A		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.52-20836G>A		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37712 AN: 151174 Hom.: 5230 Cov.: 28

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.249 AC: 37738 AN: 151292 Hom.: 5233 Cov.: 28 AF XY: 0.252 AC XY: 18631 AN XY: 73830

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.285

Alfa AF: 0.249 Hom.: 8243

Bravo AF: 0.252

Asia WGS AF: 0.470 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.61
Dann	Benign	0.22

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: rs10828616; hg19: chr10-18670017;