Variant rs7415038 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000069.3(CACNA1S):c.2403T>C(p.Phe801=) variant causes a synonymous change. The variant allele was found at a frequency of 0.419 in 1,570,430 control chromosomes in the GnomAD database, including 147,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14607 hom., cov: 32)

Exomes 𝑓: 0.42 ( 133302 hom. )

Consequence

CACNA1S
NM_000069.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

CACNA1S (HGNC:1397): (calcium voltage-gated channel subunit alpha1 S) This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]

CACNA1S links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-201069559-A-G is Benign according to our data. Variant chr1-201069559-A-G is described in ClinVar as [Benign]. Clinvar id is 254814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201069559-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1S	NM_000069.3 linkuse as main transcript	c.2403T>C	p.Phe801=	synonymous_variant	18/44	ENST00000362061.4	NP_000060.2
CACNA1S	XM_005245478.4 linkuse as main transcript	c.2403T>C	p.Phe801=	synonymous_variant	18/43		XP_005245535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1S	ENST00000362061.4 linkuse as main transcript	c.2403T>C	p.Phe801=	synonymous_variant	18/44	1	NM_000069.3	ENSP00000355192	P2

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63950

AN:

151872

Hom.:

14602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.388

GnomAD3 exomes

AF:

0.333

AC:

59753

AN:

179650

Hom.:

11942

AF XY:

0.329

AC XY:

31199

AN XY:

94918

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.00295

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.419

AC:

593924

AN:

1418440

Hom.:

133302

Cov.:

AF XY:

0.411

AC XY:

288123

AN XY:

700866

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.00159

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.421

AC:

63985

AN:

151990

Hom.:

14607

Cov.:

AF XY:

0.405

AC XY:

30078

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.526

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.384

Alfa

AF:

0.436

Hom.:

12574

Bravo

AF:

0.431

Asia WGS

AF:

0.121

AC:

425

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 21, 2017	- -

Hypokalemic periodic paralysis, type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 11, 2016	- -

Malignant hyperthermia, susceptibility to, 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Feb 05, 2024	- -

Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.74

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