NM_174934.4:c.639C>T

Variant names:

• chr11-118137075-G-A
• rs72544155
• NM_174934.4:c.639C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_174934.4(SCN4B):​c.639C>T​(p.Asn213Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,613,988 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (19 hom.)
• Consequence: SCN4B NM_174934.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.30
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-118137075-G-A is Benign according to our data. Variant chr11-118137075-G-A is described in ClinVar as Benign. ClinVar VariationId is 139036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BS2: High AC in GnomAd4 at 493 Unknown,AD gene.

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.639C>T	p.Asn213Asn	synonymous	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.309C>T	p.Asn103Asn	synonymous	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.237C>T	p.Asn79Asn	synonymous	Exon 3 of 3	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.639C>T	p.Asn213Asn	synonymous	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.782C>T		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000531550.1	TSL:1	n.704C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00582

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00283 AC: 712 AN: 251438 AF XY: 0.00289

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00540

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00500 AC: 7310 AN: 1461682 Hom.: 19 Cov.: 31 AF XY: 0.00481 AC XY: 3497 AN XY: 727152

African (AFR) AF: 0.000597 AC: 20 AN: 33476

American (AMR) AF: 0.00150 AC: 67 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86254

European-Finnish (FIN) AF: 0.000842 AC: 45 AN: 53418

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.00623 AC: 6928 AN: 1111820

Other (OTH) AF: 0.00293 AC: 177 AN: 60390

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74478

African (AFR) AF: 0.00113 AC: 47 AN: 41560

American (AMR) AF: 0.00229 AC: 35 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00582 AC: 396 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00425 Hom.: 2

Bravo AF: 0.00339

EpiCase AF: 0.00529

EpiControl AF: 0.00522

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Long QT syndrome 10 (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.21
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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: rs72544155; hg19: chr11-118007790;