rs41314807

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_000219.6(KCNE1):c.*268C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 64 hom., cov: 11)

Exomes 𝑓: 0.0011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.414

Publications

1 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 21-34448977-G-A is Benign according to our data. Variant chr21-34448977-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 339766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00114 (203/177378) while in subpopulation AFR AF = 0.0195 (127/6514). AF 95% confidence interval is 0.0167. There are 1 homozygotes in GnomAdExome4. There are 84 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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	Effect	Exon Rank	Protein	UniProt
KCNE1	NM_000219.6	MANE Select	c.*268C>T	3_prime_UTR	Exon 4 of 4	NP_000210.2	P15382
KCNE1	NM_001127668.4		c.*268C>T	3_prime_UTR	Exon 3 of 3	NP_001121140.1	P15382
KCNE1	NM_001127669.4		c.*268C>T	3_prime_UTR	Exon 3 of 3	NP_001121141.1	C7S316

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.*268C>T	3_prime_UTR	Exon 4 of 4	ENSP00000382226.2	P15382
KCNE1	ENST00000399289.7	TSL:1	c.*268C>T	3_prime_UTR	Exon 3 of 3	ENSP00000382228.3	P15382
KCNE1	ENST00000432085.5	TSL:1	c.*268C>T	3_prime_UTR	Exon 3 of 3	ENSP00000412498.1	P15382

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

918

AN:

87990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00627

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00481

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00114

AC:

203

AN:

177378

Hom.:

Cov.:

AF XY:

0.000924

AC XY:

AN XY:

90880

show subpopulations

African (AFR)

AF:

0.0195

AC:

127

AN:

6514

American (AMR)

AF:

0.00226

AC:

AN:

7510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5872

East Asian (EAS)

AF:

0.00

AC:

AN:

12056

South Asian (SAS)

AF:

0.00

AC:

AN:

13008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11346

Middle Eastern (MID)

AF:

0.00360

AC:

AN:

834

European-Non Finnish (NFE)

AF:

0.000174

AC:

AN:

108968

Other (OTH)

AF:

0.00328

AC:

AN:

11270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0104

AC:

919

AN:

88102

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

409

AN XY:

42088

show subpopulations

African (AFR)

AF:

0.0316

AC:

850

AN:

26930

American (AMR)

AF:

0.00625

AC:

AN:

8476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2074

East Asian (EAS)

AF:

0.00

AC:

AN:

2462

South Asian (SAS)

AF:

0.00

AC:

AN:

2470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5550

Middle Eastern (MID)

AF:

0.00532

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

38360

Other (OTH)

AF:

0.00982

AC:

AN:

1120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00490

Hom.:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital long QT syndrome (1)

Jervell and Lange-Nielsen syndrome 2 (1)

Long QT syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.59

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over