10-18439030-C-G

Position:

• chr10-18439030-C-G

Variant summary

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

The NM_201596.3(CACNB2):​c.333+36987C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,198 control chromosomes in the GnomAD database, including 5,987 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 0.27 (5987 hom., cov: 34)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201590.3	c.171+36987C>G		intron_variant		ENST00000377329.10	NP_963884.2
CACNB2	NM_201596.3	c.333+36987C>G		intron_variant		ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.333+36987C>G		intron_variant		1	NM_201596.3	ENSP00000320025
CACNB2	ENST00000377329.10	c.171+36987C>G		intron_variant		1	NM_201590.3	ENSP00000366546

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41313 AN: 152080 Hom.: 5989 Cov.: 34

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.272 AC: 41329 AN: 152198 Hom.: 5987 Cov.: 34 AF XY: 0.264 AC XY: 19655 AN XY: 74390

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.303

Alfa AF: 0.273 Hom.: 3195

Bravo AF: 0.275

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
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: rs12258967; hg19: chr10-18727959;