Variant chr10-18141037-G-C 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 ENST00000282343.13(CACNB2):c.-143G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,543,294 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

CACNB2
ENST00000282343.13 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.316

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:

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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=-0.7).

BP6

Variant 10-18141037-G-C is Benign according to our data. Variant chr10-18141037-G-C is described in ClinVar as [Benign]. Clinvar id is 1238565.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 = 0.0133 (2031/152274) while in subpopulation AFR AF= 0.0458 (1905/41554). AF 95% confidence interval is 0.0441. There are 50 homozygotes in gnomad4. There are 961 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2031 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.120+181G>C		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13 linkuse as main transcript	c.120+181G>C		intron_variant		1	NM_201596.3		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2021

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0144

GnomAD4 exome

AF:

0.00145

AC:

2015

AN:

1391020

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

901

AN XY:

685452

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.0000403

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000218

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.0133

AC:

2031

AN:

152274

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

961

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0458

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.70

CADD

Benign

5.9

DANN

Benign

0.92

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