rs34503140

Positions:

chr10-18539535-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000324631.13(CACNB2):c.1794T>C(p.Ser598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,613,426 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 15 hom., cov: 30)

Exomes 𝑓: 0.0035 ( 102 hom. )

Consequence

CACNB2
ENST00000324631.13 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.384

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 10-18539535-T-C is Benign according to our data. Variant chr10-18539535-T-C is described in ClinVar as [Benign]. Clinvar id is 299566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18539535-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.384 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00852 (1291/151592) while in subpopulation SAS AF= 0.0337 (160/4752). AF 95% confidence interval is 0.0294. There are 15 homozygotes in gnomad4. There are 675 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1291 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.1794T>C	p.Ser598=	synonymous_variant	14/14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3 linkuse as main transcript	c.1632T>C	p.Ser544=	synonymous_variant	13/13	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNB2	ENST00000324631.13 linkuse as main transcript	c.1794T>C	p.Ser598=	synonymous_variant	14/14	1	NM_201596.3	ENSP00000320025	Q08289-1
CACNB2	ENST00000377329.10 linkuse as main transcript	c.1632T>C	p.Ser544=	synonymous_variant	13/13	1	NM_201590.3	ENSP00000366546	Q08289-3
	ENST00000425669.1 linkuse as main transcript	n.377-236A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1287

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0113

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.00408

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00747

AC:

1877

AN:

251312

Hom.:

AF XY:

0.00877

AC XY:

1191

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00877

Gnomad SAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.00518

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00352

AC:

5143

AN:

1461834

Hom.:

102

Cov.:

AF XY:

0.00446

AC XY:

3241

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0104

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.00449

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.00469

GnomAD4 genome

AF:

0.00852

AC:

1291

AN:

151592

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

675

AN XY:

74046

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0113

Gnomad4 SAS

AF:

0.0337

Gnomad4 FIN

AF:

0.00408

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00824

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Brugada syndrome 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 05, 2020	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.0

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over