dbSNP rs729245: CACNB2:c.334-45490T>C (chr10-18452865-T-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.334-45490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,150 control chromosomes in the GnomAD database, including 34,005 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 0.66 ( 34005 hom., cov: 33)

Consequence

CACNB2
NM_201596.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0110

Publications

6 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.334-45490T>C		intron_variant	Intron 3 of 13	ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 link	c.172-45490T>C		intron_variant	Intron 2 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.334-45490T>C		intron_variant	Intron 3 of 13	1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 link	c.172-45490T>C		intron_variant	Intron 2 of 12	1	NM_201590.3	ENSP00000366546.4		Q08289-3

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100668

AN:

152032

Hom.:

34001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.659

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

GnomAD4 genome

AF:

0.662

AC:

100715

AN:

152150

Hom.:

34005

Cov.:

AF XY:

0.663

AC XY:

49340

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.556

AC:

23058

AN:

41484

American (AMR)

AF:

0.667

AC:

10197

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2120

AN:

3470

East Asian (EAS)

AF:

0.465

AC:

2410

AN:

5182

South Asian (SAS)

AF:

0.741

AC:

3571

AN:

4820

European-Finnish (FIN)

AF:

0.749

AC:

7942

AN:

10598

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.722

AC:

49122

AN:

67996

Other (OTH)

AF:

0.652

AC:

1378

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.690

Hom.:

98740

Bravo

AF:

0.645

Asia WGS

AF:

0.592

AC:

2059

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.49

PhyloP100

-0.011

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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