11-118134531-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_174934.4(SCN4B):c.*2496C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 454,030 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (24 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (8 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-118134531-G-A is Benign according to our data. Variant chr11-118134531-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 302597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1528/152234) while in subpopulation AFR AF= 0.0344 (1429/41526). AF 95% confidence interval is 0.0329. There are 24 homozygotes in gnomad4. There are 756 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1525 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN4B	NM_174934.4	c.*2496C>T		3_prime_UTR_variant	5/5	ENST00000324727.9
SCN4B	NM_001142348.2	c.*2496C>T		3_prime_UTR_variant	3/3
SCN4B	NM_001142349.2	c.*2496C>T		3_prime_UTR_variant	4/4
SCN4B	NR_024527.2	n.3172C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4B	ENST00000324727.9	c.*2496C>T		3_prime_UTR_variant	5/5	1	NM_174934.4	P1
SCN4B	ENST00000415030.6	n.3326C>T		non_coding_transcript_exon_variant	4/4	1
SCN4B	ENST00000423160.2	n.2817C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1525 AN: 152116 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00239 AC: 312 AN: 130482 Hom.: 7 AF XY: 0.00181 AC XY: 129 AN XY: 71224

Gnomad AFR exome AF: 0.0368

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.000123

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00157 AC: 473 AN: 301796 Hom.: 8 Cov.: 0 AF XY: 0.00118 AC XY: 203 AN XY: 171996

Gnomad4 AFR exome AF: 0.0362

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.0000927

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.0100 AC: 1528 AN: 152234 Hom.: 24 Cov.: 32 AF XY: 0.0102 AC XY: 756 AN XY: 74436

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00409 Hom.: 1

Bravo AF: 0.0112

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
Dann	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs114345754; hg19: chr11-118005246;