12-48824388-A-G

Position:

• chr12-48824388-A-G

Variant summary

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

The NM_000725.4(CACNB3):​c.407+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,584,958 control chromosomes in the GnomAD database, including 273,385 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 (34467 hom., cov: 30)
  • Exomes 𝑓: 0.57 (238918 hom.)
• Consequence: CACNB3 NM_000725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

CACNB3 (HGNC:1403): (calcium voltage-gated channel auxiliary subunit beta 3) This gene encodes a regulatory beta subunit of the voltage-dependent calcium channel. Beta subunits are composed of five domains, which contribute to the regulation of surface expression and gating of calcium channels and may also play a role in the regulation of transcription factors and calcium transport. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB3	NM_000725.4	c.407+15A>G		intron_variant		ENST00000301050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB3	ENST00000301050.7	c.407+15A>G		intron_variant		1	NM_000725.4	P1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99878 AN: 151726 Hom.: 34408 Cov.: 30

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.621

GnomAD3 exomes AF: 0.584 AC: 123608 AN: 211546 Hom.: 36885 AF XY: 0.573 AC XY: 64850 AN XY: 113222

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.429

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.573 AC: 821549 AN: 1433114 Hom.: 238918 Cov.: 31 AF XY: 0.570 AC XY: 404540 AN XY: 710262

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.659 AC: 99999 AN: 151844 Hom.: 34467 Cov.: 30 AF XY: 0.658 AC XY: 48840 AN XY: 74206

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.621

Alfa AF: 0.584 Hom.: 43797

Bravo AF: 0.665

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2070615; hg19: chr12-49218171; COSMIC: COSV56397552; COSMIC: COSV56397552;