rs7069292

Variant names:

• chr10-18258059-C-T
• rs7069292
• NM_201596.3:c.213+107084C>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+107084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,102 control chromosomes in the GnomAD database, including 39,935 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 0.72 (39935 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• 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

CACNB2-AS2 (HGNC:58169):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 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.213+107084C>T		intron	N/A	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.213+107084C>T		intron	N/A	NP_963891.1	Q08289-8
	CACNB2	NM_201571.4		c.129+107084C>T		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.213+107084C>T		intron	N/A	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.213+107084C>T		intron	N/A	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000282343.13	TSL:1	c.129+107084C>T		intron	N/A	ENSP00000282343.8	Q08289-4

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109717 AN: 151984 Hom.: 39908 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.722 AC: 109790 AN: 152102 Hom.: 39935 Cov.: 32 AF XY: 0.720 AC XY: 53529 AN XY: 74346

African (AFR) AF: 0.758 AC: 31437 AN: 41492

American (AMR) AF: 0.719 AC: 10990 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4981 AN: 5160

South Asian (SAS) AF: 0.587 AC: 2824 AN: 4814

European-Finnish (FIN) AF: 0.707 AC: 7478 AN: 10580

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46824 AN: 67976

Other (OTH) AF: 0.754 AC: 1595 AN: 2114

Alfa AF: 0.705 Hom.: 7715

Bravo AF: 0.729

Asia WGS AF: 0.723 AC: 2512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.37
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: rs7069292; hg19: chr10-18546988;