9-137878012-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000718.4(CACNA1B):​c.79G>T​(p.Gly27Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000133 in 149,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000035 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1B
NM_000718.4 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 4.11
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 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1BNM_000718.4 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 47 ENST00000371372.6 NP_000709.1 Q00975-1
CACNA1BNM_001243812.2 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 47 NP_001230741.1 Q00975-2
LOC100133077NR_121583.1 linkn.2692-2332C>A intron_variant Intron 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1BENST00000371372.6 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 47 5 NM_000718.4 ENSP00000360423.1 Q00975-1
CACNA1BENST00000371357.5 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 46 5 ENSP00000360408.1 B1AQK7
CACNA1BENST00000371363.5 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 46 5 ENSP00000360414.1 B1AQK6
CACNA1BENST00000277551.6 linkc.79G>T p.Gly27Cys missense_variant Exon 1 of 47 5 ENSP00000277551.2 Q00975-2

Frequencies

GnomAD3 genomes
AF:
0.0000133
AC:
2
AN:
149938
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000486
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000352
AC:
38
AN:
1079592
Hom.:
0
Cov.:
32
AF XY:
0.0000445
AC XY:
23
AN XY:
516540
show subpopulations
Gnomad4 AFR exome
AF:
0.00154
Gnomad4 AMR exome
AF:
0.000130
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:
0.00000110
Gnomad4 OTH exome
AF:
0.0000722
GnomAD4 genome
AF:
0.0000133
AC:
2
AN:
149938
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
73098
show subpopulations
Gnomad4 AFR
AF:
0.0000486
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000234
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:2
Uncertain significance, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Uncertain significance, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingNew York Genome CenterSep 04, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
.;.;T;T;.;T
Eigen
Benign
-0.075
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.62
T;T;T;T;T;T
M_CAP
Pathogenic
0.96
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D
MetaSVM
Uncertain
0.069
D
MutationAssessor
Pathogenic
3.1
M;.;M;.;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.5
N;.;N;N;N;N
REVEL
Uncertain
0.52
Sift
Uncertain
0.018
D;.;D;D;D;D
Sift4G
Uncertain
0.037
D;D;D;D;D;D
Polyphen
0.99
.;.;.;D;.;.
Vest4
0.55
MVP
0.87
MPC
1.7
ClinPred
0.89
D
GERP RS
0.65
Varity_R
0.28
gMVP
0.40

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: rs758563303; hg19: chr9-140772464; API