9-137878025-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000718.4(CACNA1B):​c.92G>T​(p.Gly31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 150,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00017 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1B
NM_000718.4 missense

Scores

1
6
11

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.854
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0054852366).
BP6
Variant 9-137878025-G-T is Benign according to our data. Variant chr9-137878025-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137878025-G-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00436 (655/150358) while in subpopulation AFR AF= 0.0147 (607/41326). AF 95% confidence interval is 0.0137. There are 1 homozygotes in gnomad4. There are 302 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 655 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1BNM_000718.4 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 47 ENST00000371372.6 NP_000709.1 Q00975-1
CACNA1BNM_001243812.2 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 47 NP_001230741.1 Q00975-2
LOC100133077NR_121583.1 linkn.2692-2345C>A intron_variant Intron 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1BENST00000371372.6 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 47 5 NM_000718.4 ENSP00000360423.1 Q00975-1
CACNA1BENST00000371357.5 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 46 5 ENSP00000360408.1 B1AQK7
CACNA1BENST00000371363.5 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 46 5 ENSP00000360414.1 B1AQK6
CACNA1BENST00000277551.6 linkc.92G>T p.Gly31Val missense_variant Exon 1 of 47 5 ENSP00000277551.2 Q00975-2

Frequencies

GnomAD3 genomes
AF:
0.00437
AC:
657
AN:
150250
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0148
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00192
Gnomad ASJ
AF:
0.000580
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000104
Gnomad OTH
AF:
0.00486
GnomAD3 exomes
AF:
0.0122
AC:
748
AN:
61328
Hom.:
1
AF XY:
0.0120
AC XY:
423
AN XY:
35120
show subpopulations
Gnomad AFR exome
AF:
0.0224
Gnomad AMR exome
AF:
0.00850
Gnomad ASJ exome
AF:
0.00990
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0115
Gnomad FIN exome
AF:
0.0129
Gnomad NFE exome
AF:
0.0139
Gnomad OTH exome
AF:
0.0145
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000166
AC:
186
AN:
1118290
Hom.:
1
Cov.:
32
AF XY:
0.000159
AC XY:
86
AN XY:
539428
show subpopulations
Gnomad4 AFR exome
AF:
0.00476
Gnomad4 AMR exome
AF:
0.00120
Gnomad4 ASJ exome
AF:
0.000131
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000428
Gnomad4 OTH exome
AF:
0.000573
GnomAD4 genome
AF:
0.00436
AC:
655
AN:
150358
Hom.:
1
Cov.:
34
AF XY:
0.00411
AC XY:
302
AN XY:
73418
show subpopulations
Gnomad4 AFR
AF:
0.0147
Gnomad4 AMR
AF:
0.00192
Gnomad4 ASJ
AF:
0.000580
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000104
Gnomad4 OTH
AF:
0.00481
Alfa
AF:
0.00788
Hom.:
7
ExAC
AF:
0.00221
AC:
193

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CACNA1B: PP3, BS1 -

Apr 29, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
.;.;T;T;.;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.59
T;T;T;T;T;T
MetaRNN
Benign
0.0055
T;T;T;T;T;T
MetaSVM
Uncertain
0.058
D
MutationAssessor
Benign
0.58
N;.;N;.;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.1
N;.;N;N;N;N
REVEL
Uncertain
0.32
Sift
Uncertain
0.025
D;.;T;T;T;T
Sift4G
Uncertain
0.022
D;D;D;D;D;D
Polyphen
0.012
.;.;.;B;.;.
Vest4
0.27
MPC
0.94
ClinPred
0.011
T
GERP RS
1.3
Varity_R
0.16
gMVP
0.38

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: rs201253748; hg19: chr9-140772477; COSMIC: COSV53138791; COSMIC: COSV53138791; API