chr21-34449551-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000219.6(KCNE1):c.84G>A(p.Ser28Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 967,632 control chromosomes in the GnomAD database, including 3,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000219.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00655 AC: 529AN: 80758Hom.: 157 Cov.: 12
GnomAD3 exomes AF: 0.00362 AC: 909AN: 251306Hom.: 1 AF XY: 0.00355 AC XY: 482AN XY: 135858
GnomAD4 exome AF: 0.0120 AC: 10604AN: 886830Hom.: 3714 Cov.: 21 AF XY: 0.0115 AC XY: 5110AN XY: 442666
GnomAD4 genome AF: 0.00652 AC: 527AN: 80802Hom.: 156 Cov.: 12 AF XY: 0.00591 AC XY: 233AN XY: 39418
ClinVar
Submissions by phenotype
not provided Benign:7
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Variant summary: The KCNE1 c.84G>A (p.Ser28Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. This variant was found in 438/120954 control chromosomes at a frequency of 0.0036212, which is approximately 362 times the estimated maximal expected allele frequency of a pathogenic KCNE1 variant (0.00001), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign and multiple publications have classified the variant as "normal/polymorphism". Taken together, this variant is classified as benign. -
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ENSG00000276289: BP4, BP7; KCNE1: BP4, BP7 -
not specified Benign:4
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Ser28Ser in Exon 03 of KCNE1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.6% (40/7020) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17173510). -
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Long QT syndrome 5 Benign:1Other:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Long QT syndrome 5;C2676723:Jervell and Lange-Nielsen syndrome 2 Benign:1
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Jervell and Lange-Nielsen syndrome 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Long QT syndrome Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at