11-118134530-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_174934.4(SCN4B):c.*2497G>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 0.000784 in 454,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd at 257 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*2497G>A		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*2497G>A		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*2497G>A		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3173G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*2497G>A		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.3327G>A		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.2818G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 257 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000529 AC: 69 AN: 130482 Hom.: 1 AF XY: 0.000351 AC XY: 25 AN XY: 71224

Gnomad AFR exome AF: 0.00558

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000383

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000331 AC: 100 AN: 301796 Hom.: 0 Cov.: 0 AF XY: 0.000227 AC XY: 39 AN XY: 171996

Gnomad4 AFR exome AF: 0.00514

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000434

Gnomad4 SAS exome AF: 0.000184

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.000214

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.00171 AC XY: 127 AN XY: 74468

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital long QT syndrome Uncertain:1

Uncertain significance, 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	-0.85
Cadd	Benign	7.4
Dann	Benign	0.40

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: rs181429015; hg19: chr11-118005245; COSMIC: COSV61253113; COSMIC: COSV61253113;