rs955917

chr11-118145324-G-Achr11-118145324-G-C

Variant summary

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

The NM_174934.4(SCN4B):c.62-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,578,992 control chromosomes in the GnomAD database, including 21,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1806 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19910 hom.)
• Consequence: SCN4B NM_174934.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0850

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=-0.88).
• BP6: Variant 11-118145324-G-A is Benign according to our data. Variant chr11-118145324-G-A is described in ClinVar as [Benign]. Clinvar id is 403418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.62-95C>T		intron_variant		ENST00000324727.9
SCN4B	NM_001142349.2	c.-364C>T		5_prime_UTR_variant	1/4
SCN4B	NM_001142348.2	c.62-3988C>T		intron_variant
SCN4B	NR_024527.2	n.110C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.62-95C>T		intron_variant		1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.110C>T		non_coding_transcript_exon_variant	1/4	1
SCN4B	ENST00000529878.1	c.62-3988C>T		intron_variant		4
SCN4B	ENST00000532138.1	n.377C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22959 AN: 152112 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.157 AC: 30591 AN: 195032 Hom.: 2370 AF XY: 0.161 AC XY: 17122 AN XY: 106388

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.161

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.165 AC: 235799 AN: 1426762 Hom.: 19910 Cov.: 33 AF XY: 0.165 AC XY: 117150 AN XY: 708038

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.151 AC: 22958 AN: 152230 Hom.: 1806 Cov.: 32 AF XY: 0.150 AC XY: 11196 AN XY: 74444

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.172

Alfa AF: 0.170 Hom.: 1270

Bravo AF: 0.152

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 25, 2016

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: 276/2178= 12.6% -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.9
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs955917; hg19: chr11-118016039; COSMIC: COSV61252849; COSMIC: COSV61252849;