10-18285383-T-C

Variant names:

• chr10-18285383-T-C
• rs1277738
• NM_201596.3:c.214-116541T>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.214-116541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,034 control chromosomes in the GnomAD database, including 19,712 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 0.50 (19712 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 6 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: Ambry Genetics, Genomics England PanelApp, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• cardiogenetic disease

  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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.214-116541T>C		intron	N/A	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.214-116541T>C		intron	N/A	NP_963891.1	Q08289-8
	CACNB2	NM_201571.4		c.130-116541T>C		intron	N/A	NP_963865.2	Q08289-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.214-116541T>C		intron	N/A	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.214-116541T>C		intron	N/A	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000282343.13	TSL:1	c.130-116541T>C		intron	N/A	ENSP00000282343.8	Q08289-4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75890 AN: 151916 Hom.: 19673 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.500 AC: 75982 AN: 152034 Hom.: 19712 Cov.: 32 AF XY: 0.500 AC XY: 37117 AN XY: 74306

African (AFR) AF: 0.627 AC: 26001 AN: 41452

American (AMR) AF: 0.538 AC: 8221 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5170

South Asian (SAS) AF: 0.568 AC: 2740 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4397 AN: 10560

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29987 AN: 67960

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.466 Hom.: 40920

Bravo AF: 0.511

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.35
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: rs1277738; hg19: chr10-18574312;