rs17173508
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000219.6(KCNE1):c.162C>T(p.Phe54Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,204,316 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 16)
Exomes 𝑓: 0.00011 ( 4 hom. )
Consequence
KCNE1
NM_000219.6 synonymous
NM_000219.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.17
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 21-34449473-G-A is Benign according to our data. Variant chr21-34449473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34449473-G-A is described in Lovd as [Benign]. Variant chr21-34449473-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 AD,AR,Digenic gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000116 AC: 12AN: 103564Hom.: 0 Cov.: 16
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GnomAD3 exomes AF: 0.000473 AC: 119AN: 251428Hom.: 1 AF XY: 0.000471 AC XY: 64AN XY: 135910
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GnomAD4 exome AF: 0.000114 AC: 125AN: 1100674Hom.: 4 Cov.: 22 AF XY: 0.000113 AC XY: 63AN XY: 558634
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GnomAD4 genome AF: 0.000106 AC: 11AN: 103642Hom.: 0 Cov.: 16 AF XY: 0.000140 AC XY: 7AN XY: 50048
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 31, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 17, 2015 | Phe54Phe in Exon 03 of KCNE1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.5% (42/8646) of East Asian chromosomes including 1 homozygote by the Exome Aggregation Consortium (E xAC, http://exac.broadinstitute.org; dbSNP rs17173508). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Long QT syndrome 5 Benign:1Other:1
not provided, no classification provided | in vitro | Roden Lab, Vanderbilt University Medical Center | - | - - |
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Jervell and Lange-Nielsen syndrome 2 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Long QT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2017 | 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at