11-118133415-AAATAC-A

Variant names:

• chr11-118133415-AAATAC-A
• rs569520041
• NM_174934.4:c.*3607_*3611delGTATT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_174934.4(SCN4B):​c.*3607_*3611delGTATT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 415,652 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.16
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 11-118133415-AAATAC-A is Benign according to our data. Variant chr11-118133415-AAATAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 302582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 352 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.*3607_*3611delGTATT		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*3607_*3611delGTATT		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*3607_*3611delGTATT		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.*3607_*3611delGTATT		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.4437_4441delGTATT		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.3928_3932delGTATT		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152224 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00174 AC: 190 AN: 109214 AF XY: 0.00189

Gnomad AFR exome AF: 0.000173

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.000646

Gnomad EAS exome AF: 0.000102

Gnomad FIN exome AF: 0.0128

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00205 AC: 540 AN: 263310 Hom.: 3 AF XY: 0.00184 AC XY: 271 AN XY: 147620

African (AFR) AF: 0.000418 AC: 3 AN: 7182

American (AMR) AF: 0.00231 AC: 51 AN: 22088

Ashkenazi Jewish (ASJ) AF: 0.000558 AC: 5 AN: 8964

East Asian (EAS) AF: 0.000116 AC: 1 AN: 8632

South Asian (SAS) AF: 0.000719 AC: 39 AN: 54222

European-Finnish (FIN) AF: 0.0129 AC: 147 AN: 11362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 962

European-Non Finnish (NFE) AF: 0.00193 AC: 266 AN: 137700

Other (OTH) AF: 0.00230 AC: 28 AN: 12198

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152342 Hom.: 2 Cov.: 32 AF XY: 0.00282 AC XY: 210 AN XY: 74500

African (AFR) AF: 0.000313 AC: 13 AN: 41576

American (AMR) AF: 0.00373 AC: 57 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00197 AC: 134 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00142

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs569520041; hg19: chr11-118004130;