chr10-18539734-G-A

Variant names:

• chr10-18539734-G-A
• rs4747352
• NM_201596.3:c.*10G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_201596.3(CACNB2):​c.*10G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,430,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CACNB2 NM_201596.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• Brugada syndrome 4

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• short QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000240291 (HGNC:58168):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-18539734-G-A is Benign according to our data. Variant chr10-18539734-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 379618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 6 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.*10G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.*10G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.*10G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.*10G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00000466 AC: 1 AN: 214756 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1430664 Hom.: 0 Cov.: 46 AF XY: 0.00000562 AC XY: 4 AN XY: 711264

African (AFR) AF: 0.000127 AC: 4 AN: 31426

American (AMR) AF: 0.00 AC: 0 AN: 37752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25066

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 80352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101980

Other (OTH) AF: 0.0000170 AC: 1 AN: 58918

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 56311

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2016

GeneDx

Significance: Likely 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	-0.86
CADD	Benign	5.3
DANN	Benign	0.87
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs4747352; hg19: chr10-18828663;