rs200963514

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_000219.6(KCNE1):c.94C>T(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 939,432 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000015 ( 4 hom. )

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 1.33

Publications

2 publications found

Variant links:

Genes affected

KCNE1 (HGNC:6240): (potassium voltage-gated channel subfamily E regulatory subunit 1) The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

KCNE1 Gene-Disease associations (from GenCC):

long QT syndrome 5
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Jervell and Lange-Nielsen syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KCNE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM1

In a mutagenesis_site Increase in inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609. (size 0) in uniprot entity KCNE1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.2682593).

BS2

High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000219.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNE1	NM_000219.6	MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 4 of 4	NP_000210.2	P15382
KCNE1	NM_001127668.4		c.94C>T	p.Arg32Cys	missense	Exon 3 of 3	NP_001121140.1	P15382
KCNE1	NM_001127669.4		c.94C>T	p.Arg32Cys	missense	Exon 3 of 3	NP_001121141.1	C7S316

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 4 of 4	ENSP00000382226.2	P15382
KCNE1	ENST00000399289.7	TSL:1	c.94C>T	p.Arg32Cys	missense	Exon 3 of 3	ENSP00000382228.3	P15382
KCNE1	ENST00000416357.6	TSL:1	c.94C>T	p.Arg32Cys	missense	Exon 2 of 2	ENSP00000416258.2	P15382

Frequencies

GnomAD3 genomes

AF:

0.0000124

AC:

AN:

80624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000261

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251346

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

858766

Hom.:

Cov.:

AF XY:

0.0000211

AC XY:

AN XY:

427508

show subpopulations

African (AFR)

AF:

0.000118

AC:

AN:

17010

American (AMR)

AF:

0.00

AC:

AN:

29374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14334

East Asian (EAS)

AF:

0.00

AC:

AN:

20110

South Asian (SAS)

AF:

0.00

AC:

AN:

49776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3498

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

653392

Other (OTH)

AF:

0.00

AC:

AN:

35178

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 Hom

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:

0.0000124

AC:

AN:

80666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

39360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18796

American (AMR)

AF:

0.00

AC:

AN:

8934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1740

East Asian (EAS)

AF:

0.00

AC:

AN:

2202

South Asian (SAS)

AF:

0.00

AC:

AN:

2316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

38296

Other (OTH)

AF:

0.00

AC:

AN:

1110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Cardiovascular phenotype (1)

Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

Eigen

Benign

0.0078

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.27

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.6

PhyloP100

1.3

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

REVEL

Pathogenic

0.78

Sift

Uncertain

0.015

Sift4G

Benign

0.15

Polyphen

0.023

Vest4

0.29

MutPred

0.50

Loss of disorder (P = 0.0242)

MVP

0.95

MPC

0.46

ClinPred

0.62

GERP RS

3.9

Varity_R

0.13

gMVP

0.57

Mutation Taster

=1/99

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over