Variant 17-63971875-A-G 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 ENST00000435607.3(SCN4A):c.483-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,612,722 control chromosomes in the GnomAD database, including 780,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74182 hom., cov: 29)

Exomes 𝑓: 0.98 ( 706059 hom. )

Consequence

SCN4A
ENST00000435607.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.453

Variant links:

Genes affected

SCN4A (HGNC:10591): (sodium voltage-gated channel alpha subunit 4) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders. [provided by RefSeq, Jul 2008]

SCN4A 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 17-63971875-A-G is Benign according to our data. Variant chr17-63971875-A-G is described in ClinVar as [Benign]. Clinvar id is 255856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63971875-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN4A	NM_000334.4 linkuse as main transcript	c.483-25T>C		intron_variant		ENST00000435607.3	NP_000325.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN4A	ENST00000435607.3 linkuse as main transcript	c.483-25T>C		intron_variant		1	NM_000334.4	ENSP00000396320	P1

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150084

AN:

151964

Hom.:

74124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.991

Gnomad FIN

AF:

0.970

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.982

Gnomad OTH

AF:

0.989

GnomAD3 exomes

AF:

0.988

AC:

244116

AN:

247158

Hom.:

120560

AF XY:

0.988

AC XY:

132666

AN XY:

134288

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

0.996

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.983

Gnomad OTH exome

AF:

0.988

GnomAD4 exome

AF:

0.983

AC:

1436122

AN:

1460640

Hom.:

706059

Cov.:

AF XY:

0.984

AC XY:

714827

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.997

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.973

Gnomad4 NFE exome

AF:

0.981

Gnomad4 OTH exome

AF:

0.985

GnomAD4 genome

AF:

0.988

AC:

150201

AN:

152082

Hom.:

74182

Cov.:

AF XY:

0.988

AC XY:

73399

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.992

Gnomad4 ASJ

AF:

0.994

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.991

Gnomad4 FIN

AF:

0.970

Gnomad4 NFE

AF:

0.982

Gnomad4 OTH

AF:

0.989

Alfa

AF:

0.987

Hom.:

13609

Bravo

AF:

0.990

Asia WGS

AF:

0.998

AC:

3470

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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