Genetic Variant NM_000219.6: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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Jervell and Lange-Nielsen syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
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
KCNE1	NM_000219.6	MANE Select	c.*124A>G	3_prime_UTR	Exon 4 of 4	NP_000210.2
KCNE1	NM_001127668.4		c.*124A>G	3_prime_UTR	Exon 3 of 3	NP_001121140.1
KCNE1	NM_001127669.4		c.*124A>G	3_prime_UTR	Exon 3 of 3	NP_001121141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.*124A>G	3_prime_UTR	Exon 4 of 4	ENSP00000382226.2
KCNE1	ENST00000399289.7	TSL:1	c.*124A>G	3_prime_UTR	Exon 3 of 3	ENSP00000382228.3
KCNE1	ENST00000432085.5	TSL:1	c.*124A>G	3_prime_UTR	Exon 3 of 3	ENSP00000412498.1

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 as Germline

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

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.5

(source)

DANN

Benign

0.69

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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