Variant rs1546416 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000069.3(CACNA1S):c.5227-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,602,084 control chromosomes in the GnomAD database, including 98,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10014 hom., cov: 33)

Exomes 𝑓: 0.35 ( 88237 hom. )

Consequence

CACNA1S
NM_000069.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.347

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-201040428-A-G is Benign according to our data. Variant chr1-201040428-A-G is described in ClinVar as [Benign]. Clinvar id is 678243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201040428-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 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.5227-54T>C		intron_variant		ENST00000362061.4	NP_000060.2
LOC101929305	XR_922410.3 linkuse as main transcript	n.1378-1427A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1S	ENST00000362061.4 linkuse as main transcript	c.5227-54T>C		intron_variant		1	NM_000069.3	ENSP00000355192	P2
	ENST00000415359.1 linkuse as main transcript	n.211-1427A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54438

AN:

152026

Hom.:

9989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.347

AC:

503038

AN:

1449940

Hom.:

88237

Cov.:

AF XY:

0.344

AC XY:

247925

AN XY:

721354

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.358

AC:

54508

AN:

152144

Hom.:

10014

Cov.:

AF XY:

0.355

AC XY:

26437

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.262

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.351

Hom.:

12310

Bravo

AF:

0.361

Asia WGS

AF:

0.308

AC:

1073

AN:

3478

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	clinical testing	GeneDx	Jun 18, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypokalemic periodic paralysis, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.90

DANN

Benign

0.53

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