11-118133973-A-G

Variant names:

• chr11-118133973-A-G
• rs3741315
• NM_174934.4:c.*3054T>C

Variant summary

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

The NM_174934.4(SCN4B):​c.*3054T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 454,308 control chromosomes in the GnomAD database, including 84,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27391 hom., cov: 32)
  • Exomes 𝑓: 0.61 (57450 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-118133973-A-G is Benign according to our data. Variant chr11-118133973-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 302585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 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.*3054T>C		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*3054T>C		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*3054T>C		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.*3054T>C		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.3884T>C		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.3375T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91078 AN: 151846 Hom.: 27360 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.605

GnomAD2 exomes AF: 0.603 AC: 79774 AN: 132190 AF XY: 0.615

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.632

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.591

GnomAD4 exome AF: 0.613 AC: 185481 AN: 302344 Hom.: 57450 Cov.: 0 AF XY: 0.624 AC XY: 107470 AN XY: 172270

African (AFR) AF: 0.624 AC: 5338 AN: 8554

American (AMR) AF: 0.519 AC: 14149 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 6530 AN: 10784

East Asian (EAS) AF: 0.645 AC: 5936 AN: 9208

South Asian (SAS) AF: 0.703 AC: 41923 AN: 59648

European-Finnish (FIN) AF: 0.573 AC: 7404 AN: 12932

Middle Eastern (MID) AF: 0.650 AC: 748 AN: 1150

European-Non Finnish (NFE) AF: 0.599 AC: 95149 AN: 158750

Other (OTH) AF: 0.591 AC: 8304 AN: 14044

GnomAD4 genome AF: 0.600 AC: 91168 AN: 151964 Hom.: 27391 Cov.: 32 AF XY: 0.601 AC XY: 44640 AN XY: 74272

African (AFR) AF: 0.622 AC: 25760 AN: 41432

American (AMR) AF: 0.540 AC: 8256 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3342 AN: 5168

South Asian (SAS) AF: 0.697 AC: 3345 AN: 4800

European-Finnish (FIN) AF: 0.567 AC: 5985 AN: 10552

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.594 AC: 40328 AN: 67942

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.589 Hom.: 36282

Bravo AF: 0.597

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital long QT syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.65
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: rs3741315; hg19: chr11-118004688;