chr11-118134907-T-G

Variant names:

• chr11-118134907-T-G
• rs45460396
• NM_174934.4:c.*2120A>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.*2120A>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 0.276 in 453,936 control chromosomes in the GnomAD database, including 19,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5594 hom., cov: 32)
  • Exomes 𝑓: 0.29 (14222 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.241
• Publications: 7 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=-0.6).
• BP6: Variant 11-118134907-T-G is Benign according to our data. Variant chr11-118134907-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 302604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 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.*2120A>C		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*2120A>C		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*2120A>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.*2120A>C		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.2950A>C		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.2441A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36930 AN: 152020 Hom.: 5593 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.264 AC: 34445 AN: 130498 AF XY: 0.264

Gnomad AFR exome AF: 0.0588

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.0513

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.293 AC: 88496 AN: 301798 Hom.: 14222 Cov.: 0 AF XY: 0.288 AC XY: 49449 AN XY: 171996

African (AFR) AF: 0.0692 AC: 592 AN: 8554

American (AMR) AF: 0.262 AC: 7154 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 2957 AN: 10786

East Asian (EAS) AF: 0.0594 AC: 547 AN: 9210

South Asian (SAS) AF: 0.218 AC: 12974 AN: 59650

European-Finnish (FIN) AF: 0.362 AC: 4472 AN: 12368

Middle Eastern (MID) AF: 0.235 AC: 270 AN: 1150

European-Non Finnish (NFE) AF: 0.350 AC: 55632 AN: 158764

Other (OTH) AF: 0.278 AC: 3898 AN: 14042

GnomAD4 genome AF: 0.243 AC: 36937 AN: 152138 Hom.: 5594 Cov.: 32 AF XY: 0.240 AC XY: 17832 AN XY: 74368

African (AFR) AF: 0.0711 AC: 2953 AN: 41524

American (AMR) AF: 0.246 AC: 3762 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3470

East Asian (EAS) AF: 0.0628 AC: 325 AN: 5172

South Asian (SAS) AF: 0.209 AC: 1011 AN: 4828

European-Finnish (FIN) AF: 0.349 AC: 3687 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23402 AN: 67976

Other (OTH) AF: 0.238 AC: 502 AN: 2106

Alfa AF: 0.260 Hom.: 1547

Bravo AF: 0.227

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.60
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		0.24
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: rs45460396; hg19: chr11-118005622;