rs727503101
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000219.6(KCNE1):āc.174C>Gā(p.Thr58Thr) variant causes a synonymous 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.000017 ( 0 hom., cov: 17)
Exomes š: 0.000076 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNE1
NM_000219.6 synonymous
NM_000219.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0280
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 Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 21-34449461-G-C is Benign according to our data. Variant chr21-34449461-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 163728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34449461-G-C is described in Lovd as [Benign]. Variant chr21-34449461-G-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.028 with no splicing effect.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000172 AC: 2AN: 116432Hom.: 0 Cov.: 17
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135906
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000758 AC: 87AN: 1147528Hom.: 0 Cov.: 19 AF XY: 0.0000722 AC XY: 42AN XY: 581558
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GnomAD4 genome AF: 0.0000172 AC: 2AN: 116432Hom.: 0 Cov.: 17 AF XY: 0.0000178 AC XY: 1AN XY: 56054
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ClinVar
Significance: Likely benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 05, 2014 | Thr58Thr in exon 3 of KCNE1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 19, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Long QT syndrome 5 Other:1
not provided, no classification provided | in vitro | Roden Lab, Vanderbilt University Medical Center | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at