rs199473348

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000219.6(KCNE1):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A8G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000097 ( 0 hom., cov: 13)

Exomes 𝑓: 0.00010 ( 7 hom. )

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:8O:1

Conservation

PhyloP100: 1.19

Publications

14 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08138129).

BS2

High Homozygotes in GnomAdExome4 at 7 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.23C>T	p.Ala8Val	missense	Exon 4 of 4	NP_000210.2	P15382
KCNE1	NM_001127668.4		c.23C>T	p.Ala8Val	missense	Exon 3 of 3	NP_001121140.1	P15382
KCNE1	NM_001127669.4		c.23C>T	p.Ala8Val	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.23C>T	p.Ala8Val	missense	Exon 4 of 4	ENSP00000382226.2	P15382
KCNE1	ENST00000399289.7	TSL:1	c.23C>T	p.Ala8Val	missense	Exon 3 of 3	ENSP00000382228.3	P15382
KCNE1	ENST00000416357.6	TSL:1	c.23C>T	p.Ala8Val	missense	Exon 2 of 2	ENSP00000416258.2	P15382

Frequencies

GnomAD3 genomes

AF:

0.0000969

AC:

AN:

92872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000874

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000359

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000931

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

251178

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

AN:

795706

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

409650

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

19648

American (AMR)

AF:

0.0000818

AC:

AN:

36682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19120

East Asian (EAS)

AF:

0.000120

AC:

AN:

33344

South Asian (SAS)

AF:

0.000250

AC:

AN:

63974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3814

European-Non Finnish (NFE)

AF:

0.0000946

AC:

AN:

539168

Other (OTH)

AF:

0.000106

AC:

AN:

37712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000968

AC:

AN:

92948

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

44890

show subpopulations

African (AFR)

AF:

0.0000870

AC:

AN:

22980

American (AMR)

AF:

0.000200

AC:

AN:

9996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2072

East Asian (EAS)

AF:

0.00

AC:

AN:

2704

South Asian (SAS)

AF:

0.000361

AC:

AN:

2770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.0000931

AC:

AN:

42946

Other (OTH)

AF:

0.00

AC:

AN:

1286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000146

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (2)

Long QT syndrome (2)

not specified (2)

Long QT syndrome 5 (1)

Long QT syndrome 5;C2676723:Jervell and Lange-Nielsen syndrome 2 (1)

Congenital long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.69

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.57

M_CAP

Benign

0.047

MetaRNN

Benign

0.081

MetaSVM

Uncertain

-0.077

MutationAssessor

Uncertain

2.6

PhyloP100

1.2

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.53

Sift

Benign

0.034

Sift4G

Benign

0.095

Polyphen

0.0030

Vest4

0.19

MVP

0.79

MPC

0.079

ClinPred

0.022

GERP RS

0.94

Varity_R

0.018

gMVP

0.45

Mutation Taster

=0/100

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over