NM_174934.4:c.*3279G>A

Variant names:

• chr11-118133748-C-T
• rs145392070
• NM_174934.4:c.*3279G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_174934.4(SCN4B):​c.*3279G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 454,530 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (12 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-118133748-C-T is Benign according to our data. Variant chr11-118133748-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 302584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 275 AD,Unknown 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.*3279G>A		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*3279G>A		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*3279G>A		3_prime_UTR	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.*3279G>A		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.4109G>A		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.3600G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00320 AC: 437 AN: 136674 AF XY: 0.00368

Gnomad AFR exome AF: 0.000622

Gnomad AMR exome AF: 0.00184

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.0000952

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.00246

Gnomad OTH exome AF: 0.00337

GnomAD4 exome AF: 0.00382 AC: 1154 AN: 302228 Hom.: 12 Cov.: 0 AF XY: 0.00447 AC XY: 770 AN XY: 172258

African (AFR) AF: 0.000818 AC: 7 AN: 8554

American (AMR) AF: 0.00180 AC: 49 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00269 AC: 29 AN: 10786

East Asian (EAS) AF: 0.000109 AC: 1 AN: 9210

South Asian (SAS) AF: 0.00944 AC: 563 AN: 59650

European-Finnish (FIN) AF: 0.000782 AC: 10 AN: 12792

Middle Eastern (MID) AF: 0.00522 AC: 6 AN: 1150

European-Non Finnish (NFE) AF: 0.00275 AC: 437 AN: 158766

Other (OTH) AF: 0.00370 AC: 52 AN: 14046

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74476

African (AFR) AF: 0.000409 AC: 17 AN: 41552

American (AMR) AF: 0.00183 AC: 28 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00248 AC: 169 AN: 68018

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00225 Hom.: 0

Bravo AF: 0.00176

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.62
DANN	Benign	0.83
PhyloP100		-1.5
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: rs145392070; hg19: chr11-118004463;