11-118133748-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_174934.4(SCN4B):c.*3279G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 454,530 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (12 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-118133748-C-T is Benign according to our data. Variant chr11-118133748-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 302584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 276 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*3279G>A		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*3279G>A		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*3279G>A		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3955G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*3279G>A		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.4109G>A		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.3600G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00320 AC: 437 AN: 136674 Hom.: 7 AF XY: 0.00368 AC XY: 273 AN XY: 74198

Gnomad AFR exome AF: 0.000622

Gnomad AMR exome AF: 0.00184

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.0000952

Gnomad SAS exome AF: 0.00965

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.00246

Gnomad OTH exome AF: 0.00337

GnomAD4 exome AF: 0.00382 AC: 1154 AN: 302228 Hom.: 12 Cov.: 0 AF XY: 0.00447 AC XY: 770 AN XY: 172258

Gnomad4 AFR exome AF: 0.000818

Gnomad4 AMR exome AF: 0.00180

Gnomad4 ASJ exome AF: 0.00269

Gnomad4 EAS exome AF: 0.000109

Gnomad4 SAS exome AF: 0.00944

Gnomad4 FIN exome AF: 0.000782

Gnomad4 NFE exome AF: 0.00275

Gnomad4 OTH exome AF: 0.00370

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74476

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00220 Hom.: 0

Bravo AF: 0.00176

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.78
Cadd	Benign	0.62
Dann	Benign	0.83

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: rs145392070; hg19: chr11-118004463;