rs1793137

Variant names:

• chr11-118145353-C-T
• rs1793137
• NM_174934.4:c.62-124G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142349.2(SCN4B):​c.-393G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,546,390 control chromosomes in the GnomAD database, including 313,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31425 hom., cov: 32)
  • Exomes 𝑓: 0.63 (282311 hom.)
• Consequence: SCN4B NM_001142349.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.527

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-118145353-C-T is Benign according to our data. Variant chr11-118145353-C-T is described in ClinVar as [Benign]. Clinvar id is 403419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4B	NM_174934.4	c.62-124G>A		intron_variant	Intron 1 of 4	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142349.2	c.-393G>A		5_prime_UTR_variant	Exon 1 of 4		NP_001135821.1
SCN4B	NM_001142348.2	c.62-4017G>A		intron_variant	Intron 1 of 2		NP_001135820.1
SCN4B	NR_024527.2	n.81G>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9	c.62-124G>A		intron_variant	Intron 1 of 4	1	NM_174934.4	ENSP00000322460.4
SCN4B	ENST00000415030.6	n.81G>A		non_coding_transcript_exon_variant	Exon 1 of 4	1
SCN4B	ENST00000529878.1	c.62-4017G>A		intron_variant	Intron 1 of 2	4		ENSP00000436343.1
SCN4B	ENST00000532138.1	n.348G>A		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97474 AN: 151850 Hom.: 31423 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.672

GnomAD3 exomes AF: 0.662 AC: 103959 AN: 156998 Hom.: 34555 AF XY: 0.659 AC XY: 56320 AN XY: 85472

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.836

Gnomad SAS exome AF: 0.632

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.637

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.635 AC: 884835 AN: 1394422 Hom.: 282311 Cov.: 41 AF XY: 0.635 AC XY: 438028 AN XY: 689766

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.699

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.561

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.642 AC: 97515 AN: 151968 Hom.: 31425 Cov.: 32 AF XY: 0.642 AC XY: 47699 AN XY: 74270

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.675

Alfa AF: 0.648 Hom.: 49697

Bravo AF: 0.654

Asia WGS AF: 0.714 AC: 2486 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in1000Genomes: 1490/2178= 68.4% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs1793137; hg19: chr11-118016068;