rs777325450

Variant names:

• chr12-48824700-A-G
• NM_000725.4:c.439A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-48824700-A-G
• chr12-48824700-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000725.4(CACNB3):​c.439A>G​(p.Ile147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I147F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CACNB3 NM_000725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06672239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB3	NM_000725.4	c.439A>G	p.Ile147Val	missense_variant	Exon 5 of 13	ENST00000301050.7	NP_000716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB3	ENST00000301050.7	c.439A>G	p.Ile147Val	missense_variant	Exon 5 of 13	1	NM_000725.4	ENSP00000301050.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461494 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.069	.;.;.;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.55	.;.;.;N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.070	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.60	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	.;.;.;B;.
Vest4		0.13
MutPred		0.25		.;.;Gain of catalytic residue at S152 (P = 0.0243);Gain of catalytic residue at S152 (P = 0.0243);.;
MVP		0.60
MPC		0.36
ClinPred		0.34	T
GERP RS		4.5
Varity_R		0.034
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49218483;