11-118145324-G-A

Variant names:

• chr11-118145324-G-A
• rs955917
• NM_174934.4:c.62-95C>T

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.-364C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,578,992 control chromosomes in the GnomAD database, including 21,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1806 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19910 hom.)
• Consequence: SCN4B NM_001142349.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0850
• Publications: 8 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: Unknown, AD Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BP6: Variant 11-118145324-G-A is Benign according to our data. Variant chr11-118145324-G-A is described in ClinVar as Benign. ClinVar VariationId is 403418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 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.62-95C>T		intron	N/A	NP_777594.1
	SCN4B	NM_001142349.2		c.-364C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001135821.1
	SCN4B	NM_001142349.2		c.-364C>T		5_prime_UTR	Exon 1 of 4	NP_001135821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN4B	ENST00000324727.9	TSL:1 MANE Select	c.62-95C>T		intron	N/A	ENSP00000322460.4
	SCN4B	ENST00000415030.6	TSL:1	n.110C>T		non_coding_transcript_exon	Exon 1 of 4
	SCN4B	ENST00000529878.1	TSL:4	c.62-3988C>T		intron	N/A	ENSP00000436343.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22959 AN: 152112 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.157 AC: 30591 AN: 195032 AF XY: 0.161

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.165 AC: 235799 AN: 1426762 Hom.: 19910 Cov.: 33 AF XY: 0.165 AC XY: 117150 AN XY: 708038

African (AFR) AF: 0.125 AC: 4083 AN: 32684

American (AMR) AF: 0.113 AC: 4561 AN: 40188

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5282 AN: 25624

East Asian (EAS) AF: 0.115 AC: 4370 AN: 38084

South Asian (SAS) AF: 0.161 AC: 13347 AN: 83030

European-Finnish (FIN) AF: 0.123 AC: 5359 AN: 43714

Middle Eastern (MID) AF: 0.258 AC: 1229 AN: 4766

European-Non Finnish (NFE) AF: 0.171 AC: 187596 AN: 1099338

Other (OTH) AF: 0.168 AC: 9972 AN: 59334

GnomAD4 genome AF: 0.151 AC: 22958 AN: 152230 Hom.: 1806 Cov.: 32 AF XY: 0.150 AC XY: 11196 AN XY: 74444

African (AFR) AF: 0.126 AC: 5218 AN: 41548

American (AMR) AF: 0.143 AC: 2181 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.105 AC: 542 AN: 5178

South Asian (SAS) AF: 0.147 AC: 711 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1296 AN: 10602

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11546 AN: 67992

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.168 Hom.: 1735

Bravo AF: 0.152

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.88
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs955917; hg19: chr11-118016039; COSMIC: COSV61252849; COSMIC: COSV61252849;