dbSNP rs2070357: KCNE1:c.*124A>G (chr21-34449121-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000219.6(KCNE1):c.*124A>G 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.171

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-34449121-T-C is Benign according to our data. Variant chr21-34449121-T-C is described in ClinVar as Benign. ClinVar VariationId is 339769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.*124A>G	3_prime_UTR	Exon 4 of 4	NP_000210.2	P15382
KCNE1	NM_001127668.4		c.*124A>G	3_prime_UTR	Exon 3 of 3	NP_001121140.1	P15382
KCNE1	NM_001127669.4		c.*124A>G	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.*124A>G	3_prime_UTR	Exon 4 of 4	ENSP00000382226.2	P15382
KCNE1	ENST00000399289.7	TSL:1	c.*124A>G	3_prime_UTR	Exon 3 of 3	ENSP00000382228.3	P15382
KCNE1	ENST00000432085.5	TSL:1	c.*124A>G	3_prime_UTR	Exon 3 of 3	ENSP00000412498.1	P15382

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111266

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

377738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

199884

African (AFR)

AF:

0.00

AC:

AN:

12978

American (AMR)

AF:

0.00

AC:

AN:

22014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10222

East Asian (EAS)

AF:

0.00

AC:

AN:

23718

South Asian (SAS)

AF:

0.00

AC:

AN:

37158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1946

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

213024

Other (OTH)

AF:

0.00

AC:

AN:

20648

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54012

African (AFR)

AF:

0.00

AC:

AN:

34520

American (AMR)

AF:

0.00

AC:

AN:

11106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2426

East Asian (EAS)

AF:

0.00

AC:

AN:

3166

South Asian (SAS)

AF:

0.00

AC:

AN:

3292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

46730

Other (OTH)

AF:

0.00

AC:

AN:

1458

Alfa

AF:

0.445

Hom.:

9859

Bravo

AF:

0.0268

Asia WGS

AF:

0.449

AC:

1560

AN:

3478

ClinVar

ClinVar submissions

Significance: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

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over