11-118134050-T-C

Variant summary

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

The NM_174934.4(SCN4B):c.*2977A>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 0.000493 in 454,562 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 0.00038 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00055 (0 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.10

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=-0.87).
• BS2: High AC in GnomAd at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*2977A>G		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*2977A>G		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*2977A>G		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3653A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*2977A>G		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.3807A>G		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.3298A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000555 AC: 73 AN: 131550 Hom.: 0 AF XY: 0.000602 AC XY: 43 AN XY: 71468

Gnomad AFR exome AF: 0.000161

Gnomad AMR exome AF: 0.000574

Gnomad ASJ exome AF: 0.000123

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000580

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000833

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000549 AC: 166 AN: 302274 Hom.: 0 Cov.: 0 AF XY: 0.000615 AC XY: 106 AN XY: 172240

Gnomad4 AFR exome AF: 0.000117

Gnomad4 AMR exome AF: 0.000513

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000402

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000712

Gnomad4 OTH exome AF: 0.000641

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74460

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000646 Hom.: 0

Bravo AF: 0.000423

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital long QT syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome 10 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.6
Dann	Benign	0.68

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: rs369720674; hg19: chr11-118004765;