Variant 1-201110107-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000069.3(CACNA1S):c.258+57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,500,426 control chromosomes in the GnomAD database, including 67,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 7095 hom., cov: 32)

Exomes 𝑓: 0.29 ( 60210 hom. )

Consequence

CACNA1S
NM_000069.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.0420

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-201110107-C-T is Benign according to our data. Variant chr1-201110107-C-T is described in ClinVar as [Benign]. Clinvar id is 17628.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-201110107-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1S	NM_000069.3 linkuse as main transcript	c.258+57G>A		intron_variant		ENST00000362061.4
CACNA1S	XM_005245478.4 linkuse as main transcript	c.258+57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1S	ENST00000362061.4 linkuse as main transcript	c.258+57G>A		intron_variant		1	NM_000069.3	P2

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44808

AN:

151928

Hom.:

7098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.286

AC:

384991

AN:

1348380

Hom.:

60210

AF XY:

0.288

AC XY:

194752

AN XY:

676598

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.650

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.295

AC:

44810

AN:

152046

Hom.:

7095

Cov.:

AF XY:

0.299

AC XY:

22204

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.309

Alfa

AF:

0.189

Hom.:

508

Bravo

AF:

0.306

Asia WGS

AF:

0.472

AC:

1638

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Thyrotoxic periodic paralysis, susceptibility to, 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.2

DANN

Benign

0.76

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