rs780553669

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000219.6(KCNE1):​c.297C>T​(p.Val99Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. V99V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 17)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCNE1
NM_000219.6 synonymous

Scores

2

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.488
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP7
Synonymous conserved (PhyloP=-0.488 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNE1NM_000219.6 linkc.297C>T p.Val99Val synonymous_variant Exon 4 of 4 ENST00000399286.3 NP_000210.2 P15382C7S316Q6FHJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNE1ENST00000399286.3 linkc.297C>T p.Val99Val synonymous_variant Exon 4 of 4 1 NM_000219.6 ENSP00000382226.2 P15382

Frequencies

GnomAD3 genomes
Cov.:
17
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251424
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1437914
Hom.:
0
Cov.:
28
AF XY:
0.00000419
AC XY:
3
AN XY:
716816
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000386
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
17

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

Long QT syndrome 5 Other:1
-
Roden Lab, Vanderbilt University Medical Center
Significance: not provided
Review Status: no classification provided
Collection Method: in vitro

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.29
DANN
Benign
0.65

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.

Other links and lift over

dbSNP: rs780553669; hg19: chr21-35821636; API