chr9-137878037-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_000718.4(CACNA1B):c.104G>A(p.Gly35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNA1B
NM_000718.4 missense
NM_000718.4 missense
Scores
2
9
7
Clinical Significance
Conservation
PhyloP100: 2.82
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CACNA1B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3511219).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.104G>A | p.Gly35Glu | missense_variant | 1/47 | ENST00000371372.6 | |
LOC100133077 | NR_121583.1 | n.2692-2357C>T | intron_variant, non_coding_transcript_variant | ||||
CACNA1B | NM_001243812.2 | c.104G>A | p.Gly35Glu | missense_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.104G>A | p.Gly35Glu | missense_variant | 1/47 | 5 | NM_000718.4 | P4 | |
ENST00000371390.1 | n.2692-2357C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1133502Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 547520
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1133502
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
547520
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.104G>A (p.G35E) alteration is located in exon 1 (coding exon 1) of the CACNA1B gene. This alteration results from a G to A substitution at nucleotide position 104, causing the glycine (G) at amino acid position 35 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;.;.
MutationTaster
Benign
D;N;N;N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.057
.;.;.;B;.;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP
MPC
1.2
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