chr9-137878082-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000718.4(CACNA1B):c.149C>T(p.Ala50Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50S) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 8.4e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNA1B
NM_000718.4 missense
NM_000718.4 missense
Scores
9
8
1
Clinical Significance
Conservation
PhyloP100: 5.03
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;
PP2
?
Missense variant where missense usually causes diseases, CACNA1B
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.149C>T | p.Ala50Val | missense_variant | 1/47 | ENST00000371372.6 | |
LOC100133077 | NR_121583.1 | n.2692-2402G>A | intron_variant, non_coding_transcript_variant | ||||
CACNA1B | NM_001243812.2 | c.149C>T | p.Ala50Val | missense_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.149C>T | p.Ala50Val | missense_variant | 1/47 | 5 | NM_000718.4 | P4 | |
ENST00000371390.1 | n.2692-2402G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.0000172 AC: 4AN: 232136Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126292
GnomAD3 exomes
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232136
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.39e-7 AC: 1AN: 1191242Hom.: 0 Cov.: 32 AF XY: 0.00000173 AC XY: 1AN XY: 579656
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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1191242
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32
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ExAC
?
AF:
AC:
3
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 26, 2022 | The c.149C>T (p.A50V) alteration is located in exon 1 (coding exon 1) of the CACNA1B gene. This alteration results from a C to T substitution at nucleotide position 149, causing the alanine (A) at amino acid position 50 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;.;.
Vest4
MutPred
Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);
MVP
MPC
0.69
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