rs1813353

Positions:

• chr10-18418519-T-C

Variant summary

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

The NM_201596.3(CACNB2):​c.333+16476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,096 control chromosomes in the GnomAD database, including 6,934 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 0.29 (6934 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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]

CACNB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.333+16476T>C		intron_variant		ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.171+16476T>C		intron_variant		ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.333+16476T>C		intron_variant		1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.171+16476T>C		intron_variant		1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43962 AN: 151992 Hom.: 6933 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.289 AC: 43957 AN: 152096 Hom.: 6934 Cov.: 33 AF XY: 0.288 AC XY: 21414 AN XY: 74354

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.314

Alfa AF: 0.318 Hom.: 982

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.62

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: rs1813353; hg19: chr10-18707448;