rs11597670

Variant names:

• chr10-18240147-C-G
• rs11597670
• NM_201596.3:c.213+89172C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-18240147-C-G
• chr10-18240147-C-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.213+89172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,210 control chromosomes in the GnomAD database, including 379 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 0.054 (379 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.213+89172C>G		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+89172C>G		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8263 AN: 152092 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0543 AC: 8266 AN: 152210 Hom.: 379 Cov.: 32 AF XY: 0.0536 AC XY: 3993 AN XY: 74438

African (AFR) AF: 0.116 AC: 4836 AN: 41518

American (AMR) AF: 0.0438 AC: 669 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.0347 AC: 180 AN: 5188

South Asian (SAS) AF: 0.0892 AC: 431 AN: 4830

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1850 AN: 68004

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0116 Hom.: 4

Bravo AF: 0.0599

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		-0.016
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: rs11597670; hg19: chr10-18529076;