Variant 10-18140701-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_201596.3(CACNB2):c.-36G>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 0.00243 in 1,568,188 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 26 hom. )

Consequence

CACNB2
NM_201596.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0330

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:

CACNB2 (HGNC:):

CACNB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 10-18140701-G-A is Benign according to our data. Variant chr10-18140701-G-A is described in ClinVar as [Benign]. Clinvar id is 1292373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1754/152256) while in subpopulation AFR AF= 0.0393 (1634/41574). AF 95% confidence interval is 0.0377. There are 37 homozygotes in gnomad4. There are 779 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.-36G>A		5_prime_UTR_variant	1/14	ENST00000324631.13	NP_963890.2	Q08289-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631 linkuse as main transcript	c.-36G>A		5_prime_UTR_variant	1/14	1	NM_201596.3	ENSP00000320025.8		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1752

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00314

AC:

593

AN:

188872

Hom.:

AF XY:

0.00273

AC XY:

283

AN XY:

103494

show subpopulations

Gnomad AFR exome

AF:

0.0415

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00325

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00143

GnomAD4 exome

AF:

0.00145

AC:

2049

AN:

1415932

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

968

AN XY:

702180

show subpopulations

Gnomad4 AFR exome

AF:

0.0386

Gnomad4 AMR exome

AF:

0.00274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000245

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.0115

AC:

1754

AN:

152256

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

779

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.98

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