10-18140478-C-A

Variant names:

• chr10-18140478-C-A
• rs12764271
• NM_201596.3:c.-259C>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201596.3(CACNB2):​c.-259C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 151,846 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (560 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.864

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-18140478-C-A is Benign according to our data. Variant chr10-18140478-C-A is described in ClinVar as [Benign]. Clinvar id is 674367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.-259C>A		5_prime_UTR_variant	Exon 1 of 14	ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631	c.-259C>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11232 AN: 151736 Hom.: 560 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00893

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0777

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

GnomAD4 genome AF: 0.0740 AC: 11235 AN: 151846 Hom.: 560 Cov.: 33 AF XY: 0.0745 AC XY: 5531 AN XY: 74222

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00895

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0769

Alfa AF: 0.0776 Hom.: 76

Bravo AF: 0.0712

Asia WGS AF: 0.0460 AC: 159 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.3
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12764271; hg19: chr10-18429407;