chr10-18392006-T-C

Position:

• chr10-18392006-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.214-9918T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 150,614 control chromosomes in the GnomAD database, including 46,548 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 0.78 (46548 hom., cov: 27)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.214-9918T>C		intron_variant		ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.52-9918T>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.214-9918T>C		intron_variant		1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.52-9918T>C		intron_variant		1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 117514 AN: 150504 Hom.: 46538 Cov.: 27

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.890

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.781 AC: 117567 AN: 150614 Hom.: 46548 Cov.: 27 AF XY: 0.781 AC XY: 57298 AN XY: 73358

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.819

Alfa AF: 0.826 Hom.: 71651

Bravo AF: 0.767

Asia WGS AF: 0.910 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.17

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: rs10828623; hg19: chr10-18680935;