rs1409207

Variant names:

• chr10-18383366-A-G
• rs1409207
• NM_201596.3:c.214-18558A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-18383366-A-G
• chr10-18383366-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.214-18558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,112 control chromosomes in the GnomAD database, including 24,850 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 0.56 (24850 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.214-18558A>G		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.52-18558A>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.214-18558A>G		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.52-18558A>G		intron_variant	Intron 1 of 12	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85793 AN: 151992 Hom.: 24824 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.564 AC: 85866 AN: 152112 Hom.: 24850 Cov.: 32 AF XY: 0.570 AC XY: 42383 AN XY: 74354

African (AFR) AF: 0.530 AC: 21965 AN: 41472

American (AMR) AF: 0.515 AC: 7872 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2369 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4905 AN: 5180

South Asian (SAS) AF: 0.566 AC: 2728 AN: 4824

European-Finnish (FIN) AF: 0.667 AC: 7064 AN: 10584

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37044 AN: 67978

Other (OTH) AF: 0.595 AC: 1258 AN: 2116

Alfa AF: 0.543 Hom.: 12400

Bravo AF: 0.557

Asia WGS AF: 0.742 AC: 2577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.37
PhyloP100		0.072
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: rs1409207; hg19: chr10-18672295;