11-118133415-AAATAC-A

Position:

• chr11-118133415-AAATAC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_174934.4(SCN4B):​c.*3607_*3611del 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 302582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 352 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN4B	NM_174934.4	c.*3607_*3611del		3_prime_UTR_variant	5/5	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142348.2	c.*3607_*3611del		3_prime_UTR_variant	3/3		NP_001135820.1
SCN4B	NM_001142349.2	c.*3607_*3611del		3_prime_UTR_variant	4/4		NP_001135821.1
SCN4B	NR_024527.2	n.4283_4287del		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9	c.*3607_*3611del		3_prime_UTR_variant	5/5	1	NM_174934.4	ENSP00000322460	P1
SCN4B	ENST00000415030.6	n.4437_4441del		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.3928_3932del		non_coding_transcript_exon_variant	3/3	2

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

GnomAD3 exomes AF: 0.00174 AC: 190 AN: 109214 Hom.: 0 AF XY: 0.00189 AC XY: 112 AN XY: 59364

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 SAS exome AF: 0.000758

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

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00231

Gnomad4 ASJ exome AF: 0.000558

Gnomad4 EAS exome AF: 0.000116

Gnomad4 SAS exome AF: 0.000719

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.00193

Gnomad4 OTH exome AF: 0.00230

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

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital long QT syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs569520041; hg19: chr11-118004130;