11-118145117-G-A

Position:

chr11-118145117-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000324727.9(SCN4B):c.174C>T(p.Cys58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,614,124 control chromosomes in the GnomAD database, including 1,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 136 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1175 hom. )

Consequence

SCN4B
ENST00000324727.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

SCN4B (HGNC:10592): (sodium voltage-gated channel beta subunit 4) The protein encoded by this gene is one of several sodium channel beta subunits. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.[provided by RefSeq, Mar 2009]

SCN4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-118145117-G-A is Benign according to our data. Variant chr11-118145117-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118145117-G-A is described in Lovd as [Benign]. Variant chr11-118145117-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCN4B	NM_174934.4 linkuse as main transcript	c.174C>T	p.Cys58=	synonymous_variant	2/5	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142349.2 linkuse as main transcript	c.-157C>T		5_prime_UTR_variant	1/4		NP_001135821.1
SCN4B	NM_001142348.2 linkuse as main transcript	c.62-3781C>T		intron_variant			NP_001135820.1
SCN4B	NR_024527.2 linkuse as main transcript	n.317C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9 linkuse as main transcript	c.174C>T	p.Cys58=	synonymous_variant	2/5	1	NM_174934.4	ENSP00000322460	P1	Q8IWT1-1
SCN4B	ENST00000415030.6 linkuse as main transcript	n.317C>T		non_coding_transcript_exon_variant	1/4	1
SCN4B	ENST00000529878.1 linkuse as main transcript	c.62-3781C>T		intron_variant		4		ENSP00000436343		Q8IWT1-3
SCN4B	ENST00000532138.1 linkuse as main transcript	n.584C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

5793

AN:

152170

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0438

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0367

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0436

GnomAD3 exomes

AF:

0.0355

AC:

8929

AN:

251476

Hom.:

192

AF XY:

0.0360

AC XY:

4887

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.0300

Gnomad ASJ exome

AF:

0.0780

Gnomad EAS exome

AF:

0.0142

Gnomad SAS exome

AF:

0.0377

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0389

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0385

AC:

56309

AN:

1461836

Hom.:

1175

Cov.:

AF XY:

0.0388

AC XY:

28238

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0386

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.0816

Gnomad4 EAS exome

AF:

0.00673

Gnomad4 SAS exome

AF:

0.0383

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.0397

Gnomad4 OTH exome

AF:

0.0424

GnomAD4 genome

AF:

0.0381

AC:

5797

AN:

152288

Hom.:

136

Cov.:

AF XY:

0.0370

AC XY:

2752

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.0437

Gnomad4 ASJ

AF:

0.0761

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.0369

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0398

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0414

Hom.:

Bravo

AF:

0.0395

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0387

EpiControl

AF:

0.0416

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2011	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.74

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