Variant 17-39175529-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000723.5(CACNB1):c.1461G>A(p.Arg487Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,613,870 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 49 hom. )

Consequence

CACNB1
NM_000723.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.23

Variant links:

Genes affected

CACNB1 (HGNC:1401): (calcium voltage-gated channel auxiliary subunit beta 1) The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

CACNB1 links:

CACNB1 (HGNC:):

CACNB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-39175529-C-T is Benign according to our data. Variant chr17-39175529-C-T is described in ClinVar as [Benign]. Clinvar id is 780422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00749 (1141/152262) while in subpopulation AFR AF= 0.0164 (683/41554). AF 95% confidence interval is 0.0154. There are 8 homozygotes in gnomad4. There are 577 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB1	NM_000723.5 linkuse as main transcript	c.1461G>A	p.Arg487Arg	synonymous_variant	14/14	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNB1	ENST00000394303.8 linkuse as main transcript	c.1461G>A	p.Arg487Arg	synonymous_variant	14/14	1	NM_000723.5	ENSP00000377840.3	Q02641-1
CACNB1	ENST00000539338.6 linkuse as main transcript	n.3580G>A		non_coding_transcript_exon_variant	12/12	1
ENSG00000266101	ENST00000579256.1 linkuse as main transcript	n.274-1675C>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1140

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00285

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00492

AC:

1219

AN:

247936

Hom.:

AF XY:

0.00481

AC XY:

648

AN XY:

134726

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00618

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00322

AC:

4712

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2538

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.00644

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00646

Gnomad4 FIN exome

AF:

0.0000752

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00749

AC:

1141

AN:

152262

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

577

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00285

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00639

Hom.:

Bravo

AF:

0.00841

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00563

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.88

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