chr11-118134531-G-A

Variant names:

• chr11-118134531-G-A
• rs114345754
• NM_174934.4:c.*2496C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1528 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.*2496C>T		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*2496C>T		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*2496C>T		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.*2496C>T		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.3326C>T		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.2817C>T		non_coding_transcript_exon	Exon 3 of 3

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

GnomAD2 exomes AF: 0.00239 AC: 312 AN: 130482 AF XY: 0.00181

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 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

African (AFR) AF: 0.0362 AC: 310 AN: 8554

American (AMR) AF: 0.00268 AC: 73 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.0000927 AC: 1 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.000101 AC: 6 AN: 59650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12366

Middle Eastern (MID) AF: 0.00609 AC: 7 AN: 1150

European-Non Finnish (NFE) AF: 0.000296 AC: 47 AN: 158764

Other (OTH) AF: 0.00207 AC: 29 AN: 14042

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

African (AFR) AF: 0.0344 AC: 1429 AN: 41526

American (AMR) AF: 0.00425 AC: 65 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00415 Hom.: 1

Bravo AF: 0.0112

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.32
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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: rs114345754; hg19: chr11-118005246;