dbSNP rs13043825: KCNS1:p.Glu86Glu (chr20-45098514-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001322799.2(KCNS1):c.258G>A(p.Glu86Glu) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.39

Variant links:

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]

KCNS1 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
KCNS1	NM_001322799.2 link	c.258G>A	p.Glu86Glu	synonymous_variant	Exon 3 of 4	ENST00000537075.3	NP_001309728.1	Q96KK3A2RUL8
KCNS1	NM_002251.5 link	c.258G>A	p.Glu86Glu	synonymous_variant	Exon 4 of 5		NP_002242.2	Q96KK3A2RUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS1	ENST00000537075.3 link	c.258G>A	p.Glu86Glu	synonymous_variant	Exon 3 of 4	1	NM_001322799.2	ENSP00000445595.1		Q96KK3
KCNS1	ENST00000306117.5 link	c.258G>A	p.Glu86Glu	synonymous_variant	Exon 4 of 5	1		ENSP00000307694.1		Q96KK3

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

29984

AN:

151316

Hom.:

3807

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.250

AC XY:

168828

AN XY:

674488

show subpopulations

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.:

AF XY:

0.201

AC XY:

14914

AN XY:

74036

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over