chr10-18216594-T-A

Position:

• chr10-18216594-T-A

Variant summary

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

The NM_201596.3(CACNB2):​c.213+65619T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,806 control chromosomes in the GnomAD database, including 35,361 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 0.67 (35361 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.213+65619T>A		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+65619T>A		intron_variant		1	NM_201596.3	ENSP00000320025
	ENST00000626127.2	n.28-9800A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101127 AN: 151690 Hom.: 35356 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.666 AC: 101167 AN: 151806 Hom.: 35361 Cov.: 32 AF XY: 0.668 AC XY: 49541 AN XY: 74182

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.691

Alfa AF: 0.652 Hom.: 2229

Bravo AF: 0.651

Asia WGS AF: 0.577 AC: 2009 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	1.1
DANN	Benign	0.80

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: rs35803482; hg19: chr10-18505523;