Variant rs41315471 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.-253A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 985,752 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 127 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 75 hom. )

Consequence

KCNE1
NM_000219.6 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.244

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=-0.98).

BP6

Variant 21-34511192-T-C is Benign according to our data. Variant chr21-34511192-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 339780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34511192-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.071 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.-253A>G		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.-253A>G		5_prime_UTR_variant	2/4	1	NM_000219.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3787

AN:

152174

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0452

Gnomad SAS

AF:

0.0460

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.00326

AC:

2718

AN:

833460

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

1220

AN XY:

384966

show subpopulations

Gnomad4 AFR exome

AF:

0.0821

Gnomad4 AMR exome

AF:

0.00610

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0519

Gnomad4 SAS exome

AF:

0.0428

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.0249

AC:

3799

AN:

152292

Hom.:

127

Cov.:

AF XY:

0.0256

AC XY:

1906

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0732

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0448

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0158

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

ClinVar

Significance: Benign/Likely 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

- -

Jervell and Lange-Nielsen syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

Cadd

Benign

3.9

Dann

Benign

0.61

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