rs1554758384

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000718.4(CACNA1B):ā€‹c.5233A>Gā€‹(p.Ser1745Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CACNA1B
NM_000718.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64
Variant links:
Genes affected
CACNA1B (HGNC:1389): (calcium voltage-gated channel subunit alpha1 B) The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34095773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1BNM_000718.4 linkc.5233A>G p.Ser1745Gly missense_variant 38/47 ENST00000371372.6 NP_000709.1 Q00975-1
CACNA1BNM_001243812.2 linkc.5233A>G p.Ser1745Gly missense_variant 38/47 NP_001230741.1 Q00975-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1BENST00000371372.6 linkc.5233A>G p.Ser1745Gly missense_variant 38/475 NM_000718.4 ENSP00000360423.1 Q00975-1
CACNA1BENST00000371357.5 linkc.5230A>G p.Ser1744Gly missense_variant 37/465 ENSP00000360408.1 B1AQK7
CACNA1BENST00000371363.5 linkc.5227A>G p.Ser1743Gly missense_variant 37/465 ENSP00000360414.1 B1AQK6
CACNA1BENST00000277551.6 linkc.5233A>G p.Ser1745Gly missense_variant 38/475 ENSP00000277551.2 Q00975-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458490
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725608
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dystonia 23 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenomic Research Center, Shahid Beheshti University of Medical SciencesDec 03, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.83
.;.;D;D;.;D
Eigen
Benign
-0.13
Eigen_PC
Benign
0.053
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.80
T;T;T;T;T;T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.34
T;T;T;T;T;T
MetaSVM
Uncertain
0.56
D
MutationAssessor
Benign
1.3
L;.;L;.;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.4
N;.;N;N;N;N
REVEL
Uncertain
0.34
Sift
Benign
0.037
D;.;D;D;D;D
Sift4G
Benign
0.15
T;T;T;T;T;T
Polyphen
0.092
.;.;.;B;.;B
Vest4
0.45
MutPred
0.41
.;.;.;.;.;Loss of catalytic residue at S1744 (P = 0.0696);
MVP
0.88
MPC
1.3
ClinPred
0.62
D
GERP RS
4.7
Varity_R
0.16
gMVP
0.79

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554758384; hg19: chr9-140997173; COSMIC: COSV53121841; API