Variant 9-137877990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000718.4(CACNA1B):c.57G>A(p.Glu19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,151,934 control chromosomes in the GnomAD database, including 2,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 621 hom., cov: 34)

Exomes 𝑓: 0.15 ( 1952 hom. )

Consequence

CACNA1B
NM_000718.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.04

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 9-137877990-G-A is Benign according to our data. Variant chr9-137877990-G-A is described in ClinVar as [Benign]. Clinvar id is 1237524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CACNA1B	NM_000718.4 linkuse as main transcript	c.57G>A	p.Glu19=	synonymous_variant	1/47	ENST00000371372.6	NP_000709.1
LOC100133077	NR_121583.1 linkuse as main transcript	n.2692-2310C>T		intron_variant, non_coding_transcript_variant
CACNA1B	NM_001243812.2 linkuse as main transcript	c.57G>A	p.Glu19=	synonymous_variant	1/47		NP_001230741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1B	ENST00000371372.6 linkuse as main transcript	c.57G>A	p.Glu19=	synonymous_variant	1/47	5	NM_000718.4	ENSP00000360423	P4	Q00975-1
	ENST00000371390.1 linkuse as main transcript	n.2692-2310C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17562

AN:

148902

Hom.:

623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.00489

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.100

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.117

AC:

1322

AN:

11300

Hom.:

AF XY:

0.115

AC XY:

644

AN XY:

5594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.153

AC:

153455

AN:

1002922

Hom.:

1952

Cov.:

AF XY:

0.154

AC XY:

73141

AN XY:

474756

show subpopulations

Gnomad4 AFR exome

AF:

0.0217

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.00282

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.118

AC:

17551

AN:

149012

Hom.:

621

Cov.:

AF XY:

0.119

AC XY:

8622

AN XY:

72698

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.00491

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0617

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2020	- -

CACNA1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 01, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

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