rs7099380

Variant names:

• chr10-18260087-G-A
• rs7099380
• NM_201596.3:c.213+109112G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):​c.213+109112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,974 control chromosomes in the GnomAD database, including 25,445 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 0.57 (25445 hom., cov: 31)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 14 publications found

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

ENSG00000235020 (HGNC:58169):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.213+109112G>A		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.213+109112G>A		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87102 AN: 151856 Hom.: 25423 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.574 AC: 87165 AN: 151974 Hom.: 25445 Cov.: 31 AF XY: 0.570 AC XY: 42354 AN XY: 74278

African (AFR) AF: 0.651 AC: 26981 AN: 41424

American (AMR) AF: 0.490 AC: 7483 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2352 AN: 3466

East Asian (EAS) AF: 0.703 AC: 3637 AN: 5176

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5822 AN: 10540

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37115 AN: 67958

Other (OTH) AF: 0.619 AC: 1304 AN: 2108

Alfa AF: 0.560 Hom.: 68575

Bravo AF: 0.576

Asia WGS AF: 0.524 AC: 1819 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	0.76
DANN	Benign	0.41
PhyloP100		-0.044
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7099380; hg19: chr10-18549016;