Variant chr9-137878081-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000718.4(CACNA1B):c.148G>A(p.Ala50Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNA1B
NM_000718.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.65

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]

CACNA1B links:

ENSG00000203987 (HGNC:58213):

ENSG00000203987 links:

LOC100133077 (HGNC:):

LOC100133077 links:

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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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1B	NM_000718.4 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 47	ENST00000371372.6	NP_000709.1	Q00975-1
CACNA1B	NM_001243812.2 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 47		NP_001230741.1	Q00975-2
LOC100133077	NR_121583.1 link	n.2692-2401C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1B	ENST00000371372.6 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 47	5	NM_000718.4	ENSP00000360423.1	Q00975-1
CACNA1B	ENST00000371357.5 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 46	5		ENSP00000360408.1	B1AQK7
CACNA1B	ENST00000371363.5 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 46	5		ENSP00000360414.1	B1AQK6
CACNA1B	ENST00000277551.6 link	c.148G>A	p.Ala50Thr	missense_variant	Exon 1 of 47	5		ENSP00000277551.2	Q00975-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1190306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

579170

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

.;.;D;T;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

1.0

D;D;D;D;D;D

M_CAP

Pathogenic

0.79

MetaRNN

Uncertain

0.54

D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.4

M;.;M;.;.;.

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.0

D;.;D;D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;.;D;D;D;D

Sift4G

Benign

0.075

T;T;T;T;T;T

Polyphen

1.0

.;.;.;D;.;.

Vest4

0.46

MutPred

0.32

Gain of glycosylation at A50 (P = 0.0232);Gain of glycosylation at A50 (P = 0.0232);Gain of glycosylation at A50 (P = 0.0232);Gain of glycosylation at A50 (P = 0.0232);Gain of glycosylation at A50 (P = 0.0232);Gain of glycosylation at A50 (P = 0.0232);

MVP

0.94

MPC

0.69

ClinPred

0.99

GERP RS

3.5

Varity_R

0.75

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over