Variant 11-118133973-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_174934.4(SCN4B):c.*3054T>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 0.609 in 454,308 control chromosomes in the GnomAD database, including 84,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27391 hom., cov: 32)

Exomes 𝑓: 0.61 ( 57450 hom. )

Consequence

SCN4B
NM_174934.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.29

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-118133973-A-G is Benign according to our data. Variant chr11-118133973-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 302585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SCN4B	NM_174934.4 linkuse as main transcript	c.*3054T>C	3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2 linkuse as main transcript	c.*3054T>C	3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2 linkuse as main transcript	c.*3054T>C	3_prime_UTR_variant	4/4
SCN4B	NR_024527.2 linkuse as main transcript	n.3730T>C	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9 linkuse as main transcript	c.*3054T>C	3_prime_UTR_variant	5/5	1	NM_174934.4	P1	Q8IWT1-1
SCN4B	ENST00000415030.6 linkuse as main transcript	n.3884T>C	non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2 linkuse as main transcript	n.3375T>C	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91078

AN:

151846

Hom.:

27360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.603

AC:

79774

AN:

132190

Hom.:

24347

AF XY:

0.615

AC XY:

44061

AN XY:

71684

show subpopulations

Gnomad AFR exome

AF:

0.625

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.632

Gnomad SAS exome

AF:

0.699

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.613

AC:

185481

AN:

302344

Hom.:

57450

Cov.:

AF XY:

0.624

AC XY:

107470

AN XY:

172270

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.519

Gnomad4 ASJ exome

AF:

0.606

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.703

Gnomad4 FIN exome

AF:

0.573

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.591

GnomAD4 genome

AF:

0.600

AC:

91168

AN:

151964

Hom.:

27391

Cov.:

AF XY:

0.601

AC XY:

44640

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.603

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.697

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.588

Hom.:

27956

Bravo

AF:

0.597

Asia WGS

AF:

0.657

AC:

2283

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

DANN

Benign

0.65

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