rs6124684

Positions:

• chr20-45092852-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322799.2(KCNS1):​c.*2018G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,678 control chromosomes in the GnomAD database, including 3,795 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 (3795 hom., cov: 30)
  • Exomes 𝑓: 0.40 (0 hom.)
• Consequence: KCNS1 NM_001322799.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNS1	NM_001322799.2	c.*2018G>A		3_prime_UTR_variant	4/4	ENST00000537075.3	NP_001309728.1
KCNS1	NM_002251.5	c.*2018G>A		3_prime_UTR_variant	5/5		NP_002242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS1	ENST00000537075	c.*2018G>A		3_prime_UTR_variant	4/4	1	NM_001322799.2	ENSP00000445595.1
KCNS1	ENST00000306117	c.*2018G>A		3_prime_UTR_variant	5/5	1		ENSP00000307694.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29784 AN: 151548 Hom.: 3793 Cov.: 30

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.196 AC: 29783 AN: 151668 Hom.: 3795 Cov.: 30 AF XY: 0.196 AC XY: 14528 AN XY: 74066

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.213

Alfa AF: 0.253 Hom.: 7255

Bravo AF: 0.181

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.55

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: rs6124684; hg19: chr20-43721493;