Variant 2-166405578-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002976.4(SCN7A):c.*2A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,555,608 control chromosomes in the GnomAD database, including 8,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 976 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7545 hom. )

Consequence

SCN7A
NM_002976.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]

SCN7A links:

SCN7A (HGNC:):

SCN7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-166405578-T-G is Benign according to our data. Variant chr2-166405578-T-G is described in ClinVar as [Benign]. Clinvar id is 3056929.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN7A	NM_002976.4 linkuse as main transcript	c.*2A>C		3_prime_UTR_variant	26/26	ENST00000643258.1	NP_002967.2	Q01118

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCN7A	ENST00000643258 linkuse as main transcript	c.*2A>C	3_prime_UTR_variant	26/26		NM_002976.4	ENSP00000496114.1	Q01118
SCN7A	ENST00000441411 linkuse as main transcript	c.*2A>C	3_prime_UTR_variant	25/25	1		ENSP00000403846.2	Q01118
SCN7A	ENST00000424326.5 linkuse as main transcript	n.*2856A>C	non_coding_transcript_exon_variant	26/26	1		ENSP00000396600.1	F8WD82
SCN7A	ENST00000424326.5 linkuse as main transcript	n.*2856A>C	3_prime_UTR_variant	26/26	1		ENSP00000396600.1	F8WD82

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16475

AN:

151932

Hom.:

977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0588

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0972

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.103

AC:

21368

AN:

208214

Hom.:

1238

AF XY:

0.105

AC XY:

11712

AN XY:

111902

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0500

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0904

Gnomad NFE exome

AF:

0.0971

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0998

AC:

140118

AN:

1403558

Hom.:

7545

Cov.:

AF XY:

0.101

AC XY:

70310

AN XY:

694896

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.0544

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0912

Gnomad4 NFE exome

AF:

0.0945

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.108

AC:

16482

AN:

152050

Hom.:

976

Cov.:

AF XY:

0.106

AC XY:

7888

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0587

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0972

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0982

Hom.:

967

Bravo

AF:

0.109

Asia WGS

AF:

0.131

AC:

455

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SCN7A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.5

DANN

Benign

0.83

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