rs139719558
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000718.4(CACNA1B):c.228C>A(p.Phe76Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.
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
6
6
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.04
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.755
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 47 | ENST00000371372.6 | NP_000709.1 | |
CACNA1B | NM_001243812.2 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 47 | NP_001230741.1 | ||
LOC100133077 | NR_121583.1 | n.2692-2481G>T | intron_variant | Intron 2 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 47 | 5 | NM_000718.4 | ENSP00000360423.1 | ||
CACNA1B | ENST00000371357.5 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 46 | 5 | ENSP00000360408.1 | |||
CACNA1B | ENST00000371363.5 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 46 | 5 | ENSP00000360414.1 | |||
CACNA1B | ENST00000277551.6 | c.228C>A | p.Phe76Leu | missense_variant | Exon 1 of 47 | 5 | ENSP00000277551.2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245602Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133610
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1152904Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 555594
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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33
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ExAC
AF:
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1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;.;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.70
.;.;.;P;.;.
Vest4
MutPred
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
MPC
0.78
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