11-118134148-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.*2879T>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 0.277 in 454,150 control chromosomes in the GnomAD database, including 19,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5601 hom., cov: 33)
  • Exomes 𝑓: 0.29 (14252 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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=-0.89).
• BP6: Variant 11-118134148-A-G is Benign according to our data. Variant chr11-118134148-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 302591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*2879T>C		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*2879T>C		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*2879T>C		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3555T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*2879T>C		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.3709T>C		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.3200T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36959 AN: 152106 Hom.: 5600 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.264 AC: 34496 AN: 130674 Hom.: 5207 AF XY: 0.264 AC XY: 18822 AN XY: 71220

Gnomad AFR exome AF: 0.0584

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.0513

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.293 AC: 88609 AN: 301926 Hom.: 14252 Cov.: 0 AF XY: 0.288 AC XY: 49534 AN XY: 172056

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.0596

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.243 AC: 36967 AN: 152224 Hom.: 5601 Cov.: 33 AF XY: 0.240 AC XY: 17852 AN XY: 74418

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.240

Alfa AF: 0.277 Hom.: 1374

Bravo AF: 0.227

Asia WGS AF: 0.137 AC: 474 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	-0.89
Cadd	Benign	1.2
Dann	Benign	0.49

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: rs45584835; hg19: chr11-118004863;