rs12257556

Positions:

• chr10-18501574-G-A
• chr10-18501574-G-C
• chr10-18501574-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.593+626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,082 control chromosomes in the GnomAD database, including 27,694 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 0.59 (27694 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.431+626G>A		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.593+626G>A		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.593+626G>A		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.431+626G>A		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90316 AN: 151964 Hom.: 27648 Cov.: 33

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.595 AC: 90417 AN: 152082 Hom.: 27694 Cov.: 33 AF XY: 0.598 AC XY: 44482 AN XY: 74346

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.582

Alfa AF: 0.530 Hom.: 28104

Bravo AF: 0.601

Asia WGS AF: 0.763 AC: 2649 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.63

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: rs12257556; hg19: chr10-18790503;