12-48824388-A-G

Variant names:

• chr12-48824388-A-G
• rs2070615
• NM_000725.4:c.407+15A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000725.4. 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
	CACNB3	NM_000725.4	MANE Select	c.407+15A>G		intron	N/A	NP_000716.2
	CACNB3	NM_001206916.2		c.404+15A>G		intron	N/A	NP_001193845.1	P54284-4
	CACNB3	NM_001206917.2		c.368+15A>G		intron	N/A	NP_001193846.1	P54284-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB3	ENST00000301050.7	TSL:1 MANE Select	c.407+15A>G		intron	N/A	ENSP00000301050.2	P54284-1
	CACNB3	ENST00000536187.6	TSL:2	c.404+15A>G		intron	N/A	ENSP00000444160.2	P54284-4
	CACNB3	ENST00000861431.1		c.407+15A>G		intron	N/A	ENSP00000531490.1

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

GnomAD2 exomes AF: 0.584 AC: 123608 AN: 211546 AF XY: 0.573

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 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

African (AFR) AF: 0.878 AC: 29118 AN: 33164

American (AMR) AF: 0.657 AC: 26282 AN: 39996

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12504 AN: 25418

East Asian (EAS) AF: 0.427 AC: 16574 AN: 38842

South Asian (SAS) AF: 0.477 AC: 39271 AN: 82286

European-Finnish (FIN) AF: 0.637 AC: 32582 AN: 51118

Middle Eastern (MID) AF: 0.600 AC: 3431 AN: 5720

European-Non Finnish (NFE) AF: 0.572 AC: 627765 AN: 1097074

Other (OTH) AF: 0.572 AC: 34022 AN: 59496

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

African (AFR) AF: 0.863 AC: 35744 AN: 41412

American (AMR) AF: 0.649 AC: 9901 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2169 AN: 5136

South Asian (SAS) AF: 0.481 AC: 2316 AN: 4812

European-Finnish (FIN) AF: 0.656 AC: 6915 AN: 10546

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39283 AN: 67896

Other (OTH) AF: 0.621 AC: 1311 AN: 2112

Alfa AF: 0.596 Hom.: 106087

Bravo AF: 0.665

Asia WGS AF: 0.482 AC: 1676 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	5.3
DANN	Benign	0.58
PhyloP100		0.0040
Mutation Taster		=6/94	disease causing

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

Other links and lift over

dbSNP: rs2070615; hg19: chr12-49218171; COSMIC: COSV56397552; COSMIC: COSV56397552;