rs729245

Variant names:

• chr10-18452865-T-C
• rs729245
• NM_201596.3:c.334-45490T>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.334-45490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,150 control chromosomes in the GnomAD database, including 34,005 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 0.66 (34005 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 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.334-45490T>C		intron	N/A	NP_963890.2
	CACNB2	NM_201590.3	MANE Plus Clinical	c.172-45490T>C		intron	N/A	NP_963884.2
	CACNB2	NM_201597.3		c.334-45490T>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.334-45490T>C		intron	N/A	ENSP00000320025.8
	CACNB2	ENST00000377329.10	TSL:1 MANE Plus Clinical	c.172-45490T>C		intron	N/A	ENSP00000366546.4
	CACNB2	ENST00000352115.10	TSL:1	c.334-45490T>C		intron	N/A	ENSP00000344474.6

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100668 AN: 152032 Hom.: 34001 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.662 AC: 100715 AN: 152150 Hom.: 34005 Cov.: 33 AF XY: 0.663 AC XY: 49340 AN XY: 74386

African (AFR) AF: 0.556 AC: 23058 AN: 41484

American (AMR) AF: 0.667 AC: 10197 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2410 AN: 5182

South Asian (SAS) AF: 0.741 AC: 3571 AN: 4820

European-Finnish (FIN) AF: 0.749 AC: 7942 AN: 10598

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49122 AN: 67996

Other (OTH) AF: 0.652 AC: 1378 AN: 2114

Alfa AF: 0.690 Hom.: 98740

Bravo AF: 0.645

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.011
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: rs729245; hg19: chr10-18741794;