rs7083127

Variant names:

• chr10-18342516-A-G
• rs7083127
• NM_201596.3:c.214-59408A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-18342516-A-G
• chr10-18342516-A-T

Variant summary

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

The NM_201596.3(CACNB2):​c.214-59408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,044 control chromosomes in the GnomAD database, including 43,084 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 0.75 (43084 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.214-59408A>G		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.51+1539A>G		intron_variant	Intron 1 of 12	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-59408A>G		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.51+1539A>G		intron_variant	Intron 1 of 12	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113673 AN: 151926 Hom.: 43060 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.748 AC: 113748 AN: 152044 Hom.: 43084 Cov.: 32 AF XY: 0.739 AC XY: 54913 AN XY: 74310

African (AFR) AF: 0.837 AC: 34715 AN: 41498

American (AMR) AF: 0.677 AC: 10348 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2498 AN: 5158

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4818

European-Finnish (FIN) AF: 0.663 AC: 6976 AN: 10524

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50619 AN: 67986

Other (OTH) AF: 0.779 AC: 1643 AN: 2108

Alfa AF: 0.743 Hom.: 5840

Bravo AF: 0.754

Asia WGS AF: 0.590 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-3.1
Mutation Taster		=100/0	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: rs7083127; hg19: chr10-18631445;