rs10764566

Variant names:

• chr10-18521745-G-A
• rs10764566
• NM_201596.3:c.944+2777G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-18521745-G-A
• chr10-18521745-G-C
• chr10-18521745-G-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.944+2777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,042 control chromosomes in the GnomAD database, including 29,877 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 0.62 (29877 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 10 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

ENSG00000240291 (HGNC:58168):

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 (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.944+2777G>A		intron_variant	Intron 9 of 13	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.782+2777G>A		intron_variant	Intron 8 of 12	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.944+2777G>A		intron_variant	Intron 9 of 13	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.782+2777G>A		intron_variant	Intron 8 of 12	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93726 AN: 151924 Hom.: 29850 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.617 AC: 93800 AN: 152042 Hom.: 29877 Cov.: 32 AF XY: 0.619 AC XY: 45982 AN XY: 74306

African (AFR) AF: 0.737 AC: 30552 AN: 41474

American (AMR) AF: 0.617 AC: 9439 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3472

East Asian (EAS) AF: 0.967 AC: 5005 AN: 5176

South Asian (SAS) AF: 0.696 AC: 3348 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5431 AN: 10550

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36383 AN: 67954

Other (OTH) AF: 0.604 AC: 1277 AN: 2114

Alfa AF: 0.562 Hom.: 95207

Bravo AF: 0.627

Asia WGS AF: 0.778 AC: 2704 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	5.9
DANN	Benign	0.37
PhyloP100		0.093
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: rs10764566; hg19: chr10-18810674;