rs1793137

Variant names:

• chr11-118145353-C-T
• rs1793137
• NM_174934.4:c.62-124G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142349.2(SCN4B):​c.-393G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,546,390 control chromosomes in the GnomAD database, including 313,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31425 hom., cov: 32)
  • Exomes 𝑓: 0.63 (282311 hom.)
• Consequence: SCN4B NM_001142349.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.527
• Publications: 11 publications found

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]

SCN4B Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 10

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000296275 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-118145353-C-T is Benign according to our data. Variant chr11-118145353-C-T is described in ClinVar as Benign. ClinVar VariationId is 403419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142349.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN4B	NM_174934.4	MANE Select	c.62-124G>A		intron	N/A	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.-393G>A		5_prime_UTR	Exon 1 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.62-4017G>A		intron	N/A	NP_001135820.1	Q8IWT1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN4B	ENST00000324727.9	TSL:1 MANE Select	c.62-124G>A		intron	N/A	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.81G>A		non_coding_transcript_exon	Exon 1 of 4
	SCN4B	ENST00000529878.1	TSL:4	c.62-4017G>A		intron	N/A	ENSP00000436343.1	Q8IWT1-3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97474 AN: 151850 Hom.: 31423 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.672

GnomAD2 exomes AF: 0.662 AC: 103959 AN: 156998 AF XY: 0.659

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.836

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.637

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.635 AC: 884835 AN: 1394422 Hom.: 282311 Cov.: 41 AF XY: 0.635 AC XY: 438028 AN XY: 689766

African (AFR) AF: 0.633 AC: 20157 AN: 31826

American (AMR) AF: 0.689 AC: 25125 AN: 36488

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 17682 AN: 25282

East Asian (EAS) AF: 0.812 AC: 29360 AN: 36168

South Asian (SAS) AF: 0.632 AC: 50750 AN: 80300

European-Finnish (FIN) AF: 0.561 AC: 20754 AN: 36996

Middle Eastern (MID) AF: 0.694 AC: 2969 AN: 4280

European-Non Finnish (NFE) AF: 0.627 AC: 679795 AN: 1084914

Other (OTH) AF: 0.657 AC: 38243 AN: 58168

GnomAD4 genome AF: 0.642 AC: 97515 AN: 151968 Hom.: 31425 Cov.: 32 AF XY: 0.642 AC XY: 47699 AN XY: 74270

African (AFR) AF: 0.630 AC: 26095 AN: 41396

American (AMR) AF: 0.691 AC: 10582 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4286 AN: 5166

South Asian (SAS) AF: 0.631 AC: 3034 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6045 AN: 10550

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42739 AN: 67950

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.642 Hom.: 114738

Bravo AF: 0.654

Asia WGS AF: 0.714 AC: 2486 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1793137; hg19: chr11-118016068;