ENST00000377315.6:c.-323G>C

Variant names:

• chr10-18400709-G-C
• rs61839258
• ENST00000377315.6:c.-323G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000377315.6(CACNB2):​c.-323G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 941,556 control chromosomes in the GnomAD database, including 1 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: CACNB2 ENST00000377315.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.214-1215G>C		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.52-1215G>C		intron_variant	Intron 1 of 12	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-1215G>C		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.52-1215G>C		intron_variant	Intron 1 of 12	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000212 AC: 2 AN: 941556 Hom.: 1 Cov.: 32 AF XY: 0.00000454 AC XY: 2 AN XY: 440320

African (AFR) AF: 0.0000999 AC: 2 AN: 20028

American (AMR) AF: 0.00 AC: 0 AN: 5514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9276

East Asian (EAS) AF: 0.00 AC: 0 AN: 11572

South Asian (SAS) AF: 0.00 AC: 0 AN: 20894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831554

Other (OTH) AF: 0.00 AC: 0 AN: 34452

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		-0.037
PromoterAI		-0.063	Neutral

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: rs61839258; hg19: chr10-18689638;