chr11-118134404-T-C

Variant names:

• chr11-118134404-T-C
• rs868344
• NM_174934.4:c.*2623A>G

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.*2623A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 453,964 control chromosomes in the GnomAD database, including 19,770 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 (5569 hom., cov: 32)
  • Exomes 𝑓: 0.29 (14201 hom.)
• Consequence: SCN4B NM_174934.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.277
• Publications: 17 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=-0.92).
• BP6: Variant 11-118134404-T-C is Benign according to our data. Variant chr11-118134404-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 302594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 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.*2623A>G		3_prime_UTR	Exon 5 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.*2623A>G		3_prime_UTR	Exon 4 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.*2623A>G		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.*2623A>G		3_prime_UTR	Exon 5 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.3453A>G		non_coding_transcript_exon	Exon 4 of 4
	SCN4B	ENST00000423160.2	TSL:2	n.2944A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36525 AN: 152064 Hom.: 5568 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.263 AC: 34350 AN: 130478 AF XY: 0.264

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.0515

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.293 AC: 88379 AN: 301782 Hom.: 14201 Cov.: 0 AF XY: 0.287 AC XY: 49414 AN XY: 171986

African (AFR) AF: 0.0606 AC: 518 AN: 8554

American (AMR) AF: 0.261 AC: 7123 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 2958 AN: 10786

East Asian (EAS) AF: 0.0596 AC: 549 AN: 9210

South Asian (SAS) AF: 0.217 AC: 12969 AN: 59650

European-Finnish (FIN) AF: 0.361 AC: 4468 AN: 12366

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

European-Non Finnish (NFE) AF: 0.350 AC: 55631 AN: 158750

Other (OTH) AF: 0.277 AC: 3893 AN: 14042

GnomAD4 genome AF: 0.240 AC: 36529 AN: 152182 Hom.: 5569 Cov.: 32 AF XY: 0.237 AC XY: 17639 AN XY: 74380

African (AFR) AF: 0.0623 AC: 2590 AN: 41558

American (AMR) AF: 0.244 AC: 3726 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3468

East Asian (EAS) AF: 0.0627 AC: 325 AN: 5180

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3693 AN: 10576

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23394 AN: 67978

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.305 Hom.: 13876

Bravo AF: 0.224

Asia WGS AF: 0.138 AC: 477 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	0.26
DANN	Benign	0.61
PhyloP100		-0.28
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: rs868344; hg19: chr11-118005119;