Variant 10-18527704-C-T 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.1054+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,565,510 control chromosomes in the GnomAD database, including 29,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3200 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25934 hom. )

Consequence

CACNB2
NM_201596.3 splice_region, intron

Scores

Splicing: ADA: 0.00004690

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.332

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:

ENSG00000240291 (HGNC:58168):

ENSG00000240291 links:

LOC124902386 (HGNC:):

LOC124902386 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 10-18527704-C-T is Benign according to our data. Variant chr10-18527704-C-T is described in ClinVar as [Benign]. Clinvar id is 263263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18527704-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.1054+7C>T		splice_region_variant, intron_variant		ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 link	c.892+7C>T		splice_region_variant, intron_variant		ENST00000377329.10	NP_963884.2	Q08289-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.1054+7C>T		splice_region_variant, intron_variant		1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 link	c.892+7C>T		splice_region_variant, intron_variant		1	NM_201590.3	ENSP00000366546.4		Q08289-3

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29721

AN:

151958

Hom.:

3197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.221

AC:

55255

AN:

249746

Hom.:

7134

AF XY:

0.218

AC XY:

29406

AN XY:

135108

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.261

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.183

AC:

258839

AN:

1413432

Hom.:

25934

Cov.:

AF XY:

0.186

AC XY:

131097

AN XY:

706258

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.196

AC:

29747

AN:

152078

Hom.:

3200

Cov.:

AF XY:

0.202

AC XY:

14995

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.176

Hom.:

1751

Bravo

AF:

0.199

Asia WGS

AF:

0.305

AC:

1060

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Brugada syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0020

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