11-118134404-T-C

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.*2623A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 453,964 control chromosomes in the GnomAD database, including 19,770 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 (5569 hom., cov: 32)
  • Exomes 𝑓: 0.29 (14201 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.277

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=-0.92).
• BP6: Variant 11-118134404-T-C is Benign according to our data. Variant chr11-118134404-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 302594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*2623A>G		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*2623A>G		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*2623A>G		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3299A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*2623A>G		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.3453A>G		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.2944A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36525 AN: 152064 Hom.: 5568 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.263 AC: 34350 AN: 130478 Hom.: 5192 AF XY: 0.264 AC XY: 18772 AN XY: 71214

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.0515

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.293 AC: 88379 AN: 301782 Hom.: 14201 Cov.: 0 AF XY: 0.287 AC XY: 49414 AN XY: 171986

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.0596

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.240 AC: 36529 AN: 152182 Hom.: 5569 Cov.: 32 AF XY: 0.237 AC XY: 17639 AN XY: 74380

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.238

Alfa AF: 0.309 Hom.: 10520

Bravo AF: 0.224

Asia WGS AF: 0.138 AC: 477 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	-0.92
Cadd	Benign	0.26
Dann	Benign	0.61

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: rs868344; hg19: chr11-118005119;