Menu
GeneBe

rs111679484

Positions:

Variant summary

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

The NM_000334.4(SCN4A):​c.3720+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,603,828 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 66 hom., cov: 31)
Exomes 𝑓: 0.024 ( 584 hom. )

Consequence

SCN4A
NM_000334.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.222
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-63945350-T-C is Benign according to our data. Variant chr17-63945350-T-C is described in ClinVar as [Benign]. Clinvar id is 255849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63945350-T-C is described in Lovd as [Likely_benign]. Variant chr17-63945350-T-C is described in Lovd as [Benign].
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3304/151946) while in subpopulation NFE AF= 0.0316 (2149/67932). AF 95% confidence interval is 0.0305. There are 66 homozygotes in gnomad4. There are 1720 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd4 at 66 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCN4ANM_000334.4 linkuse as main transcriptc.3720+10A>G intron_variant ENST00000435607.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCN4AENST00000435607.3 linkuse as main transcriptc.3720+10A>G intron_variant 1 NM_000334.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0218
AC:
3303
AN:
151832
Hom.:
66
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00358
Gnomad AMI
AF:
0.00769
Gnomad AMR
AF:
0.00741
Gnomad ASJ
AF:
0.0162
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00250
Gnomad FIN
AF:
0.0747
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0316
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.0225
AC:
5499
AN:
244840
Hom.:
121
AF XY:
0.0225
AC XY:
2985
AN XY:
132678
show subpopulations
Gnomad AFR exome
AF:
0.00344
Gnomad AMR exome
AF:
0.00416
Gnomad ASJ exome
AF:
0.0170
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00230
Gnomad FIN exome
AF:
0.0776
Gnomad NFE exome
AF:
0.0299
Gnomad OTH exome
AF:
0.0205
GnomAD4 exome
AF:
0.0243
AC:
35264
AN:
1451882
Hom.:
584
Cov.:
33
AF XY:
0.0240
AC XY:
17316
AN XY:
720424
show subpopulations
Gnomad4 AFR exome
AF:
0.00285
Gnomad4 AMR exome
AF:
0.00458
Gnomad4 ASJ exome
AF:
0.0167
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00216
Gnomad4 FIN exome
AF:
0.0736
Gnomad4 NFE exome
AF:
0.0265
Gnomad4 OTH exome
AF:
0.0196
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0217
AC:
3304
AN:
151946
Hom.:
66
Cov.:
31
AF XY:
0.0232
AC XY:
1720
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.00357
Gnomad4 AMR
AF:
0.00740
Gnomad4 ASJ
AF:
0.0162
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00250
Gnomad4 FIN
AF:
0.0747
Gnomad4 NFE
AF:
0.0316
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0282
Hom.:
38
Bravo
AF:
0.0149
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, criteria provided, single submitterclinical testingGeneDxFeb 15, 2016This 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJul 21, 2017- -
Hyperkalemic periodic paralysis Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Hypokalemic periodic paralysis, type 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Paramyotonia congenita of Von Eulenburg Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Potassium-aggravated myotonia Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Congenital myasthenic syndrome 16 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
13
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs111679484; hg19: chr17-62022710; API