Variant 17-63964718-T-C 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_000334.4(SCN4A):c.1243-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,513,008 control chromosomes in the GnomAD database, including 598,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 51411 hom., cov: 32)

Exomes 𝑓: 0.89 ( 547390 hom. )

Consequence

SCN4A
NM_000334.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.254

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:

LOC105371858 (HGNC:):

LOC105371858 links:

Genome browser will be placed here

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 17-63964718-T-C is Benign according to our data. Variant chr17-63964718-T-C is described in ClinVar as [Benign]. Clinvar id is 255843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63964718-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SCN4A	NM_000334.4 linkuse as main transcript	c.1243-41A>G	intron_variant	ENST00000435607.3
LOC105371858	XR_001752969.2 linkuse as main transcript	n.345+68T>C	intron_variant, non_coding_transcript_variant
LOC105371858	XR_001752970.2 linkuse as main transcript	n.400+68T>C	intron_variant, non_coding_transcript_variant
LOC105371858	XR_934910.3 linkuse as main transcript	n.220+68T>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4A	ENST00000435607.3 linkuse as main transcript	c.1243-41A>G		intron_variant		1	NM_000334.4	P1

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122715

AN:

152048

Hom.:

51395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.973

Gnomad SAS

AF:

0.935

Gnomad FIN

AF:

0.872

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.831

GnomAD3 exomes

AF:

0.893

AC:

158714

AN:

177688

Hom.:

71624

AF XY:

0.900

AC XY:

85383

AN XY:

94902

show subpopulations

Gnomad AFR exome

AF:

0.541

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.912

Gnomad EAS exome

AF:

0.978

Gnomad SAS exome

AF:

0.932

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.899

Gnomad OTH exome

AF:

0.899

GnomAD4 exome

AF:

0.895

AC:

1217720

AN:

1360842

Hom.:

547390

Cov.:

AF XY:

0.897

AC XY:

605875

AN XY:

675328

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.931

Gnomad4 ASJ exome

AF:

0.913

Gnomad4 EAS exome

AF:

0.964

Gnomad4 SAS exome

AF:

0.930

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.900

Gnomad4 OTH exome

AF:

0.888

GnomAD4 genome

AF:

0.807

AC:

122769

AN:

152166

Hom.:

51411

Cov.:

AF XY:

0.810

AC XY:

60291

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.555

Gnomad4 AMR

AF:

0.890

Gnomad4 ASJ

AF:

0.913

Gnomad4 EAS

AF:

0.973

Gnomad4 SAS

AF:

0.935

Gnomad4 FIN

AF:

0.872

Gnomad4 NFE

AF:

0.901

Gnomad4 OTH

AF:

0.833

Alfa

AF:

0.847

Hom.:

7834

Bravo

AF:

0.797

Asia WGS

AF:

0.920

AC:

3198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.3

DANN

Benign

0.38

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