rs4748474

chr10-18501798-G-Achr10-18501798-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):c.593+850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,036 control chromosomes in the GnomAD database, including 27,984 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 0.60 (27984 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.431+850G>A		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.593+850G>A		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.593+850G>A		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.431+850G>A		intron_variant		1	NM_201590.3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90674 AN: 151918 Hom.: 27940 Cov.: 33

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.597 AC: 90772 AN: 152036 Hom.: 27984 Cov.: 33 AF XY: 0.601 AC XY: 44670 AN XY: 74304

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.579

Alfa AF: 0.526 Hom.: 19607

Bravo AF: 0.604

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.14
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs4748474; hg19: chr10-18790727;