10-18140695-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201596.3(CACNB2):c.-42C>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 0.0357 in 1,559,106 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (150 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1000 hom.)
• Consequence: CACNB2 NM_201596.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.990

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-18140695-C-A is Benign according to our data. Variant chr10-18140695-C-A is described in ClinVar as [Benign]. Clinvar id is 190719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201596.3	c.-42C>A		5_prime_UTR_variant	1/14	ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.-42C>A		5_prime_UTR_variant	1/14	1	NM_201596.3
CACNB2	ENST00000352115.10			upstream_gene_variant		1
CACNB2	ENST00000377328.5			upstream_gene_variant		1
CACNB2	ENST00000645287.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6384 AN: 152086 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0402

GnomAD3 exomes AF: 0.0326 AC: 5979 AN: 183408 Hom.: 131 AF XY: 0.0332 AC XY: 3332 AN XY: 100470

Gnomad AFR exome AF: 0.0588

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.0475

Gnomad EAS exome AF: 0.0000704

Gnomad SAS exome AF: 0.0334

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0374

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0350 AC: 49223 AN: 1406906 Hom.: 1000 Cov.: 27 AF XY: 0.0353 AC XY: 24619 AN XY: 697748

Gnomad4 AFR exome AF: 0.0611

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.0478

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.0346

Gnomad4 FIN exome AF: 0.0398

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0420 AC: 6390 AN: 152200 Hom.: 150 Cov.: 32 AF XY: 0.0413 AC XY: 3072 AN XY: 74416

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0213 Hom.: 8

Bravo AF: 0.0408

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	12
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs138094231; hg19: chr10-18429624;