dbSNP rs6124684: KCNS1:c.*2018G>A (chr20-45092852-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

16 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNS1	NM_001322799.2 link	c.*2018G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000537075.3	NP_001309728.1
KCNS1	NM_002251.5 link	c.*2018G>A		3_prime_UTR_variant	Exon 5 of 5		NP_002242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS1	ENST00000537075.3 link	c.*2018G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_001322799.2	ENSP00000445595.1
KCNS1	ENST00000306117.5 link	c.*2018G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000307694.1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29784

AN:

151548

Hom.:

3793

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29783

AN:

151668

Hom.:

3795

Cov.:

AF XY:

0.196

AC XY:

14528

AN XY:

74066

show subpopulations

African (AFR)

AF:

0.0463

AC:

1916

AN:

41368

American (AMR)

AF:

0.170

AC:

2585

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

682

AN:

3464

East Asian (EAS)

AF:

0.150

AC:

775

AN:

5154

South Asian (SAS)

AF:

0.143

AC:

686

AN:

4792

European-Finnish (FIN)

AF:

0.328

AC:

3439

AN:

10498

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.279

AC:

18958

AN:

67858

Other (OTH)

AF:

0.213

AC:

447

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1116

2233

3349

4466

5582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.233

Hom.:

10021

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

(source)

DANN

Benign

0.55

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over