rs41314071

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000219.6(KCNE1):c.*132A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 476,646 control chromosomes in the GnomAD database, including 14,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 4710 hom., cov: 16)

Exomes 𝑓: 0.085 ( 9312 hom. )

Consequence

KCNE1
NM_000219.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.148

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 21-34449113-T-C is Benign according to our data. Variant chr21-34449113-T-C is described in ClinVar as [Benign]. Clinvar id is 339768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34449113-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE1	NM_000219.6 linkuse as main transcript	c.*132A>G		3_prime_UTR_variant	4/4	ENST00000399286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE1	ENST00000399286.3 linkuse as main transcript	c.*132A>G		3_prime_UTR_variant	4/4	1	NM_000219.6	P1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

16177

AN:

110746

Hom.:

4699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.0745

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0341

Gnomad SAS

AF:

0.0733

Gnomad FIN

AF:

0.0630

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.0855

AC:

31270

AN:

365790

Hom.:

9312

Cov.:

AF XY:

0.0845

AC XY:

16306

AN XY:

193074

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.0458

Gnomad4 ASJ exome

AF:

0.0988

Gnomad4 EAS exome

AF:

0.0141

Gnomad4 SAS exome

AF:

0.0590

Gnomad4 FIN exome

AF:

0.0674

Gnomad4 NFE exome

AF:

0.0919

Gnomad4 OTH exome

AF:

0.0982

GnomAD4 genome

AF:

0.146

AC:

16213

AN:

110856

Hom.:

4710

Cov.:

AF XY:

0.141

AC XY:

7605

AN XY:

53850

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.0684

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0342

Gnomad4 SAS

AF:

0.0712

Gnomad4 FIN

AF:

0.0630

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.0928

Hom.:

540

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Long QT syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Congenital long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Jervell and Lange-Nielsen syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

Cadd

Benign

4.1

Dann

Benign

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over