dbSNP rs12240995: CACNB2:c.214-53621A>C (chr10-18348303-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_201596.3(CACNB2):c.214-53621A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,252 control chromosomes in the GnomAD database, including 1,185 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 0.12 ( 1185 hom., cov: 32)

Consequence

CACNB2
NM_201596.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.214

Publications

4 publications found

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 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

CACNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.214-53621A>C		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 link	c.51+7326A>C		intron_variant	Intron 1 of 12	ENST00000377329.10	NP_963884.2	Q08289-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.214-53621A>C		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 link	c.51+7326A>C		intron_variant	Intron 1 of 12	1	NM_201590.3	ENSP00000366546.4		Q08289-3

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18180

AN:

152134

Hom.:

1179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0373

Gnomad SAS

AF:

0.0702

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.107

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

GnomAD4 genome

AF:

0.120

AC:

18219

AN:

152252

Hom.:

1185

Cov.:

AF XY:

0.117

AC XY:

8693

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.126

AC:

5224

AN:

41528

American (AMR)

AF:

0.145

AC:

2220

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3472

East Asian (EAS)

AF:

0.0376

AC:

195

AN:

5190

South Asian (SAS)

AF:

0.0698

AC:

337

AN:

4828

European-Finnish (FIN)

AF:

0.112

AC:

1186

AN:

10604

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8371

AN:

68012

Other (OTH)

AF:

0.105

AC:

223

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

837

1674

2512

3349

4186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.122

Hom.:

1060

Bravo

AF:

0.127

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.90

(source)

DANN

Benign

0.61

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over