11-118133973-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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 -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91078 AN: 151846 Hom.: 27360 Cov.: 32

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

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.: 0 AF XY: 0.624 AC XY: 107470 AN XY: 172270

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.: 32 AF XY: 0.601 AC XY: 44640 AN XY: 74272

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: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	-0.87
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

Other links and lift over

dbSNP: rs3741315; hg19: chr11-118004688;