rs11014504

Variant names:

• chr10-18495059-T-C
• rs11014504
• NM_201596.3:c.334-3296T>C

Variant summary

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

The NM_201596.3(CACNB2):​c.334-3296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,976 control chromosomes in the GnomAD database, including 15,194 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 0.44 (15194 hom., cov: 31)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201596.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	NM_201596.3	MANE Select	c.334-3296T>C		intron	N/A	NP_963890.2
	CACNB2	NM_201590.3	MANE Plus Clinical	c.172-3296T>C		intron	N/A	NP_963884.2
	CACNB2	NM_201597.3		c.334-3296T>C		intron	N/A	NP_963891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.334-3296T>C		intron	N/A	ENSP00000320025.8
	CACNB2	ENST00000377329.10	TSL:1 MANE Plus Clinical	c.172-3296T>C		intron	N/A	ENSP00000366546.4
	CACNB2	ENST00000352115.10	TSL:1	c.334-3296T>C		intron	N/A	ENSP00000344474.6

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67249 AN: 151858 Hom.: 15197 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.443 AC: 67267 AN: 151976 Hom.: 15194 Cov.: 31 AF XY: 0.444 AC XY: 32959 AN XY: 74288

African (AFR) AF: 0.415 AC: 17194 AN: 41446

American (AMR) AF: 0.420 AC: 6417 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3613 AN: 5170

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4820

European-Finnish (FIN) AF: 0.444 AC: 4674 AN: 10524

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30130 AN: 67954

Other (OTH) AF: 0.457 AC: 968 AN: 2116

Alfa AF: 0.433 Hom.: 2558

Bravo AF: 0.441

Asia WGS AF: 0.533 AC: 1852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.83
PhyloP100		0.21
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: rs11014504; hg19: chr10-18783988;