11-118145117-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_174934.4(SCN4B):c.174C>T(p.Cys58Cys) 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
NM_174934.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.27

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
long QT syndrome 10
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
long QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SCN4B links:

ENSG00000296275 (HGNC:):

ENSG00000296275 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 139037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SCN4B	NM_174934.4 link	c.174C>T	p.Cys58Cys	synonymous_variant	Exon 2 of 5	ENST00000324727.9	NP_777594.1	Q8IWT1-1B0YJ93
SCN4B	NR_024527.2 link	n.317C>T		non_coding_transcript_exon_variant	Exon 1 of 4
SCN4B	NM_001142349.2 link	c.-157C>T		5_prime_UTR_variant	Exon 1 of 4		NP_001135821.1	Q8IWT1-2
SCN4B	NM_001142348.2 link	c.62-3781C>T		intron_variant	Intron 1 of 2		NP_001135820.1	Q8IWT1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9 link	c.174C>T	p.Cys58Cys	synonymous_variant	Exon 2 of 5	1	NM_174934.4	ENSP00000322460.4		Q8IWT1-1

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

GnomAD2 exomes

AF:

0.0355

AC:

8929

AN:

251476

AF XY:

0.0360

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 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

African (AFR)

AF:

0.0386

AC:

1293

AN:

33478

American (AMR)

AF:

0.0318

AC:

1422

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0816

AC:

2134

AN:

26136

East Asian (EAS)

AF:

0.00673

AC:

267

AN:

39700

South Asian (SAS)

AF:

0.0383

AC:

3301

AN:

86256

European-Finnish (FIN)

AF:

0.0151

AC:

806

AN:

53416

Middle Eastern (MID)

AF:

0.0579

AC:

334

AN:

5768

European-Non Finnish (NFE)

AF:

0.0397

AC:

44194

AN:

1111964

Other (OTH)

AF:

0.0424

AC:

2558

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3096

6191

9287

12382

15478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1680

3360

5040

6720

8400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0381

AC:

5797

AN:

152288

Hom.:

136

Cov.:

AF XY:

0.0370

AC XY:

2752

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0394

AC:

1639

AN:

41548

American (AMR)

AF:

0.0437

AC:

669

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3468

East Asian (EAS)

AF:

0.0151

AC:

AN:

5182

South Asian (SAS)

AF:

0.0369

AC:

178

AN:

4822

European-Finnish (FIN)

AF:

0.0125

AC:

133

AN:

10624

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0398

AC:

2707

AN:

68024

Other (OTH)

AF:

0.0436

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

286

571

857

1142

1428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0339

Hom.:

259

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 15, 2011

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Long QT syndrome 10

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Aug 07, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.74

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over