rs45539032

Variant names:

• chr11-118145117-G-A
• rs45539032
• NM_174934.4:c.174C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118145117-G-A
• chr11-118145117-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_174934.4(SCN4B):​c.174C>T​(p.Cys58Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,614,124 control chromosomes in the GnomAD database, including 1,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (136 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1175 hom.)
• Consequence: SCN4B NM_174934.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.27
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 11-118145117-G-A is Benign according to our data. Variant chr11-118145117-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.27 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174934.4. 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.174C>T	p.Cys58Cys	synonymous	Exon 2 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.-157C>T		5_prime_UTR	Exon 1 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.62-3781C>T		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.174C>T	p.Cys58Cys	synonymous	Exon 2 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.317C>T		non_coding_transcript_exon	Exon 1 of 4
	SCN4B	ENST00000529878.1	TSL:4	c.62-3781C>T		intron	N/A	ENSP00000436343.1	Q8IWT1-3

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5793 AN: 152170 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0436

GnomAD2 exomes AF: 0.0355 AC: 8929 AN: 251476 AF XY: 0.0360

Gnomad AFR exome AF: 0.0407

Gnomad AMR exome AF: 0.0300

Gnomad ASJ exome AF: 0.0780

Gnomad EAS exome AF: 0.0142

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.0389

Gnomad OTH exome AF: 0.0455

GnomAD4 exome AF: 0.0385 AC: 56309 AN: 1461836 Hom.: 1175 Cov.: 32 AF XY: 0.0388 AC XY: 28238 AN XY: 727222

African (AFR) AF: 0.0386 AC: 1293 AN: 33478

American (AMR) AF: 0.0318 AC: 1422 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2134 AN: 26136

East Asian (EAS) AF: 0.00673 AC: 267 AN: 39700

South Asian (SAS) AF: 0.0383 AC: 3301 AN: 86256

European-Finnish (FIN) AF: 0.0151 AC: 806 AN: 53416

Middle Eastern (MID) AF: 0.0579 AC: 334 AN: 5768

European-Non Finnish (NFE) AF: 0.0397 AC: 44194 AN: 1111964

Other (OTH) AF: 0.0424 AC: 2558 AN: 60394

GnomAD4 genome AF: 0.0381 AC: 5797 AN: 152288 Hom.: 136 Cov.: 32 AF XY: 0.0370 AC XY: 2752 AN XY: 74464

African (AFR) AF: 0.0394 AC: 1639 AN: 41548

American (AMR) AF: 0.0437 AC: 669 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5182

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4822

European-Finnish (FIN) AF: 0.0125 AC: 133 AN: 10624

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2707 AN: 68024

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0339 Hom.: 259

Bravo AF: 0.0395

Asia WGS AF: 0.0270 AC: 94 AN: 3478

EpiCase AF: 0.0387

EpiControl AF: 0.0416

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome 10 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.3
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: rs45539032; hg19: chr11-118015832; COSMIC: COSV107331386; COSMIC: COSV107331386;