rs17691888

chr10-18445599-G-A

Variant summary

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

The NM_201596.3(CACNB2):c.333+43556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 93,324 control chromosomes in the GnomAD database, including 884 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 0.16 (884 hom., cov: 26)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.171+43556G>A		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.333+43556G>A		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.333+43556G>A		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.171+43556G>A		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 14769 AN: 93212 Hom.: 882 Cov.: 26

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.158 AC: 14777 AN: 93324 Hom.: 884 Cov.: 26 AF XY: 0.162 AC XY: 7480 AN XY: 46132

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0884

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.186

Alfa AF: 0.0778 Hom.: 88

Bravo AF: 0.0963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.3
Dann	Benign	0.74

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: rs17691888; hg19: chr10-18734528;