rs13043825

Positions:

• chr20-45098514-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001322799.2(KCNS1):​c.258G>A​(p.Glu86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,519,866 control chromosomes in the GnomAD database, including 50,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3807 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46322 hom.)
• Consequence: KCNS1 NM_001322799.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

Genes affected

KCNS1 (HGNC:6300): (potassium voltage-gated channel modifier subfamily S member 1) Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=2.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNS1	NM_001322799.2	c.258G>A	p.Glu86=	synonymous_variant	3/4	ENST00000537075.3
KCNS1	NM_002251.5	c.258G>A	p.Glu86=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNS1	ENST00000537075.3	c.258G>A	p.Glu86=	synonymous_variant	3/4	1	NM_001322799.2	P1
KCNS1	ENST00000306117.5	c.258G>A	p.Glu86=	synonymous_variant	4/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29984 AN: 151316 Hom.: 3807 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.224 AC: 26741 AN: 119644 Hom.: 3451 AF XY: 0.221 AC XY: 14451 AN XY: 65486

Gnomad AFR exome AF: 0.0518

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.253 AC: 345675 AN: 1368440 Hom.: 46322 Cov.: 34 AF XY: 0.250 AC XY: 168828 AN XY: 674488

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.0877

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.198 AC: 29974 AN: 151426 Hom.: 3807 Cov.: 32 AF XY: 0.201 AC XY: 14914 AN XY: 74036

Gnomad4 AFR AF: 0.0501

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.219

Alfa AF: 0.244 Hom.: 1463

Bravo AF: 0.182

Asia WGS AF: 0.133 AC: 462 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.97

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: rs13043825; hg19: chr20-43727155; COSMIC: COSV60260637;