chr9-137877982-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_000718.4(CACNA1B):c.49G>A(p.Gly17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,130,022 control chromosomes in the GnomAD database, including 2,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 728 hom., cov: 33)
Exomes 𝑓: 0.16 ( 2175 hom. )
Consequence
CACNA1B
NM_000718.4 missense
NM_000718.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 2.09
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 -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CACNA1B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0010201633).
BP6
?
Variant 9-137877982-G-A is Benign according to our data. Variant chr9-137877982-G-A is described in ClinVar as [Benign]. Clinvar id is 1222494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.49G>A | p.Gly17Ser | missense_variant | 1/47 | ENST00000371372.6 | |
LOC100133077 | NR_121583.1 | n.2692-2302C>T | intron_variant, non_coding_transcript_variant | ||||
CACNA1B | NM_001243812.2 | c.49G>A | p.Gly17Ser | missense_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.49G>A | p.Gly17Ser | missense_variant | 1/47 | 5 | NM_000718.4 | P4 | |
ENST00000371390.1 | n.2692-2302C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.134 AC: 19969AN: 148528Hom.: 732 Cov.: 33
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GnomAD3 exomes AF: 0.120 AC: 1260AN: 10516Hom.: 0 AF XY: 0.119 AC XY: 626AN XY: 5240
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GnomAD4 exome AF: 0.156 AC: 152903AN: 981384Hom.: 2175 Cov.: 29 AF XY: 0.157 AC XY: 72604AN XY: 463456
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GnomAD4 genome ? AF: 0.134 AC: 19966AN: 148638Hom.: 728 Cov.: 33 AF XY: 0.134 AC XY: 9720AN XY: 72486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 31, 2019 | - - |
CACNA1B-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.13
.;.;.;B;.;.
Vest4
MPC
1.5
ClinPred
T
GERP RS
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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