chr12-48824388-A-C

Variant names:

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

Variant summary

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

The NM_000725.4(CACNB3):​c.407+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 30)
  • Exomes 𝑓: 7.0e-7 (0 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: 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).

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>C		intron	N/A	NP_000716.2
	CACNB3	NM_001206916.2		c.404+15A>C		intron	N/A	NP_001193845.1	P54284-4
	CACNB3	NM_001206917.2		c.368+15A>C		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>C		intron	N/A	ENSP00000301050.2	P54284-1
	CACNB3	ENST00000536187.6	TSL:2	c.404+15A>C		intron	N/A	ENSP00000444160.2	P54284-4
	CACNB3	ENST00000861431.1		c.407+15A>C		intron	N/A	ENSP00000531490.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000473 AC: 1 AN: 211546 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434080 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710762

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 40048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25434

East Asian (EAS) AF: 0.00 AC: 0 AN: 38862

South Asian (SAS) AF: 0.00 AC: 0 AN: 82326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51192

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097776

Other (OTH) AF: 0.00 AC: 0 AN: 59530

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.0040

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: rs2070615; hg19: chr12-49218171;