12-48824710-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000725.4(CACNB3):c.449G>A(p.Arg150Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,613,602 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 1 hom., cov: 30)
Exomes 𝑓: 0.000068 ( 2 hom. )
Consequence
CACNB3
NM_000725.4 missense
NM_000725.4 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 6.47
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.023057431).
BS2
High Homozygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB3 | NM_000725.4 | c.449G>A | p.Arg150Gln | missense_variant | 5/13 | ENST00000301050.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB3 | ENST00000301050.7 | c.449G>A | p.Arg150Gln | missense_variant | 5/13 | 1 | NM_000725.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 151616Hom.: 1 Cov.: 30
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GnomAD3 exomes AF: 0.000151 AC: 38AN: 251346Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135862
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461866Hom.: 2 Cov.: 33 AF XY: 0.0000550 AC XY: 40AN XY: 727238
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GnomAD4 genome AF: 0.000125 AC: 19AN: 151736Hom.: 1 Cov.: 30 AF XY: 0.000121 AC XY: 9AN XY: 74146
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.449G>A (p.R150Q) alteration is located in exon 5 (coding exon 5) of the CACNB3 gene. This alteration results from a G to A substitution at nucleotide position 449, causing the arginine (R) at amino acid position 150 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;.;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.98
.;.;.;D;.
Vest4
MutPred
0.35
.;.;Gain of catalytic residue at P153 (P = 5e-04);Gain of catalytic residue at P153 (P = 5e-04);.;
MVP
MPC
1.2
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at