Variant 9-137878128-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_000718.4(CACNA1B):c.195G>A(p.Lys65Lys) variant causes a synonymous 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 Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNA1B
NM_000718.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 9-137878128-G-A is Benign according to our data. Variant chr9-137878128-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770698.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1B	NM_000718.4 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 47	ENST00000371372.6	NP_000709.1	Q00975-1
CACNA1B	NM_001243812.2 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 47		NP_001230741.1	Q00975-2
LOC100133077	NR_121583.1 link	n.2692-2448C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1B	ENST00000371372.6 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 47	5	NM_000718.4	ENSP00000360423.1	Q00975-1
CACNA1B	ENST00000371357.5 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 46	5		ENSP00000360408.1	B1AQK7
CACNA1B	ENST00000371363.5 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 46	5		ENSP00000360414.1	B1AQK6
CACNA1B	ENST00000277551.6 link	c.195G>A	p.Lys65Lys	synonymous_variant	Exon 1 of 47	5		ENSP00000277551.2	Q00975-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000773

AC:

AN:

245756

Hom.:

AF XY:

0.0000973

AC XY:

AN XY:

133590

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:

0.000162

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000169

AC:

AN:

1182088

Hom.:

Cov.:

AF XY:

0.00000349

AC XY:

AN XY:

573738

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:

0.00000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000132

Hom.:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CACNA1B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over