Variant rs2834502 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000219.6(KCNE1):c.-252G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 985,406 control chromosomes in the GnomAD database, including 27,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4172 hom., cov: 32)

Exomes 𝑓: 0.23 ( 22992 hom. )

Consequence

KCNE1
NM_000219.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.268

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 21-34511191-C-T is Benign according to our data. Variant chr21-34511191-C-T is described in ClinVar as [Benign]. Clinvar id is 339779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34511191-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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.-252G>A		5_prime_UTR_variant	2/4	ENST00000399286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE1	ENST00000399286.3 linkuse as main transcript	c.-252G>A		5_prime_UTR_variant	2/4	1	NM_000219.6	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31417

AN:

152088

Hom.:

4170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.232

AC:

193398

AN:

833200

Hom.:

22992

Cov.:

AF XY:

0.231

AC XY:

88942

AN XY:

384860

show subpopulations

Gnomad4 AFR exome

AF:

0.0377

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.206

AC:

31420

AN:

152206

Hom.:

4172

Cov.:

AF XY:

0.211

AC XY:

15691

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0575

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.245

Hom.:

9399

Bravo

AF:

0.214

Asia WGS

AF:

0.329

AC:

1140

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

-0.92

CADD

Benign

3.7

DANN

Benign

0.66

Splicing

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