rs1554758384
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000718.4(CACNA1B):āc.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
NM_000718.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.64
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.5233A>G | p.Ser1745Gly | missense_variant | 38/47 | 5 | NM_000718.4 | ENSP00000360423.1 | ||
CACNA1B | ENST00000371357.5 | c.5230A>G | p.Ser1744Gly | missense_variant | 37/46 | 5 | ENSP00000360408.1 | |||
CACNA1B | ENST00000371363.5 | c.5227A>G | p.Ser1743Gly | missense_variant | 37/46 | 5 | ENSP00000360414.1 | |||
CACNA1B | ENST00000277551.6 | c.5233A>G | p.Ser1745Gly | missense_variant | 38/47 | 5 | ENSP00000277551.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458490Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725608
GnomAD4 exome
AF:
AC:
1
AN:
1458490
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
725608
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 03, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D;D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N;N;N;N
REVEL
Uncertain
Sift
Benign
D;.;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.092
.;.;.;B;.;B
Vest4
MutPred
0.41
.;.;.;.;.;Loss of catalytic residue at S1744 (P = 0.0696);
MVP
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at