Variant rs201253748 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000718.4(CACNA1B):c.92G>A(p.Gly31Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000894 in 1,118,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G31V) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

CACNA1B
NM_000718.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.854

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34517425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1B	NM_000718.4 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 47	ENST00000371372.6	NP_000709.1	Q00975-1
CACNA1B	NM_001243812.2 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 47		NP_001230741.1	Q00975-2
LOC100133077	NR_121583.1 link	n.2692-2345C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1B	ENST00000371372.6 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 47	5	NM_000718.4	ENSP00000360423.1	Q00975-1
CACNA1B	ENST00000371357.5 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 46	5		ENSP00000360408.1	B1AQK7
CACNA1B	ENST00000371363.5 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 46	5		ENSP00000360414.1	B1AQK6
CACNA1B	ENST00000277551.6 link	c.92G>A	p.Gly31Asp	missense_variant	Exon 1 of 47	5		ENSP00000277551.2	Q00975-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

61328

Hom.:

AF XY:

0.0000285

AC XY:

AN XY:

35120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000452

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.94e-7

AC:

AN:

1118592

Hom.:

Cov.:

AF XY:

0.00000185

AC XY:

AN XY:

539564

show subpopulations

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:

0.00000107

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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;.;T;T;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.59

T;T;T;T;T;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.35

T;T;T;T;T;T

MetaSVM

Uncertain

0.037

MutationAssessor

Benign

1.4

L;.;L;.;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.7

N;.;N;N;N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.019

D;.;T;T;T;T

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

0.0010

.;.;.;B;.;.

Vest4

0.28

MutPred

0.26

Loss of glycosylation at P32 (P = 0.07);Loss of glycosylation at P32 (P = 0.07);Loss of glycosylation at P32 (P = 0.07);Loss of glycosylation at P32 (P = 0.07);Loss of glycosylation at P32 (P = 0.07);Loss of glycosylation at P32 (P = 0.07);

MVP

0.80

MPC

1.4

ClinPred

0.22

GERP RS

1.3

Varity_R

0.15

gMVP

0.43

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