Variant chr10-18140695-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201596.3(CACNB2):c.-42C>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 0.0357 in 1,559,106 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 150 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1000 hom. )

Consequence

CACNB2
NM_201596.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.990

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 10-18140695-C-A is Benign according to our data. Variant chr10-18140695-C-A is described in ClinVar as [Benign]. Clinvar id is 190719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.-42C>A		5_prime_UTR_variant	1/14	ENST00000324631.13	NP_963890.2	Q08289-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNB2	ENST00000324631 link	c.-42C>A	5_prime_UTR_variant	1/14	1	NM_201596.3	ENSP00000320025.8	Q08289-1
CACNB2	ENST00000352115.10 link	c.-42C>A	upstream_gene_variant		1		ENSP00000344474.6	Q08289-8
CACNB2	ENST00000377328.5 link	c.-42C>A	upstream_gene_variant		1		ENSP00000366545.1	A6PVM6
CACNB2	ENST00000645287.2 link	c.-485C>A	upstream_gene_variant				ENSP00000496203.1	Q08289-9

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6384

AN:

152086

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.0389

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0372

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0326

AC:

5979

AN:

183408

Hom.:

131

AF XY:

0.0332

AC XY:

3332

AN XY:

100470

show subpopulations

Gnomad AFR exome

AF:

0.0588

Gnomad AMR exome

AF:

0.0192

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.0000704

Gnomad SAS exome

AF:

0.0334

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0374

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0350

AC:

49223

AN:

1406906

Hom.:

1000

Cov.:

AF XY:

0.0353

AC XY:

24619

AN XY:

697748

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.0478

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0398

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0342

GnomAD4 genome

AF:

0.0420

AC:

6390

AN:

152200

Hom.:

150

Cov.:

AF XY:

0.0413

AC XY:

3072

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0617

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0389

Gnomad4 NFE

AF:

0.0372

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0213

Hom.:

Bravo

AF:

0.0408

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2013

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.88

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