Variant rs75168694 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000334.4(SCN4A):c.1453-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,580,630 control chromosomes in the GnomAD database, including 604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.020 ( 64 hom., cov: 33)

Exomes 𝑓: 0.023 ( 540 hom. )

Consequence

SCN4A
NM_000334.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0100

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

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-63963848-G-A is Benign according to our data. Variant chr17-63963848-G-A is described in ClinVar as [Benign]. Clinvar id is 255844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63963848-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0201 (3066/152356) while in subpopulation NFE AF= 0.0318 (2162/68038). AF 95% confidence interval is 0.0307. There are 64 homozygotes in gnomad4. There are 1511 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SCN4A	NM_000334.4 linkuse as main transcript	c.1453-23C>T	intron_variant	ENST00000435607.3	NP_000325.4
LOC105371858	XR_001752969.2 linkuse as main transcript	n.119-236G>A	intron_variant, non_coding_transcript_variant
LOC105371858	XR_001752970.2 linkuse as main transcript	n.174-236G>A	intron_variant, non_coding_transcript_variant
LOC105371858	XR_934910.3 linkuse as main transcript	n.118+534G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN4A	ENST00000435607.3 linkuse as main transcript	c.1453-23C>T		intron_variant		1	NM_000334.4	ENSP00000396320	P1

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3065

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00354

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0318

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0208

AC:

4139

AN:

198914

Hom.:

AF XY:

0.0206

AC XY:

2217

AN XY:

107858

show subpopulations

Gnomad AFR exome

AF:

0.00300

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00198

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0304

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0235

AC:

33500

AN:

1428274

Hom.:

540

Cov.:

AF XY:

0.0233

AC XY:

16505

AN XY:

707620

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.00392

Gnomad4 ASJ exome

AF:

0.0244

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.0548

Gnomad4 NFE exome

AF:

0.0262

Gnomad4 OTH exome

AF:

0.0185

GnomAD4 genome

AF:

0.0201

AC:

3066

AN:

152356

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1511

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00353

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0510

Gnomad4 NFE

AF:

0.0318

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0346

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00260

AC:

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

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

DANN

Benign

0.24

BranchPoint Hunter

0.0

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