rs140024352
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_003640.5(ELP1):āc.3213G>Cā(p.Glu1071Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,613,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_003640.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.3213G>C | p.Glu1071Asp | missense_variant | 29/37 | ENST00000374647.10 | |
ELP1 | NM_001318360.2 | c.2871G>C | p.Glu957Asp | missense_variant | 29/37 | ||
ELP1 | NM_001330749.2 | c.2166G>C | p.Glu722Asp | missense_variant | 27/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.3213G>C | p.Glu1071Asp | missense_variant | 29/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000552 AC: 84AN: 152226Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000466 AC: 117AN: 251280Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135802
GnomAD4 exome AF: 0.000709 AC: 1036AN: 1461772Hom.: 1 Cov.: 31 AF XY: 0.000672 AC XY: 489AN XY: 727184
GnomAD4 genome ? AF: 0.000552 AC: 84AN: 152226Hom.: 1 Cov.: 33 AF XY: 0.000538 AC XY: 40AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 02, 2023 | The ELP1 c.3213G>C; p.Glu1071Asp variant (rs140024352), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 526197). This variant is found in the general population with an overall allele frequency of 0.05% (133/282,676 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.025). Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1071 of the ELP1 protein (p.Glu1071Asp). This variant is present in population databases (rs140024352, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 526197). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2021 | The p.E1071D variant (also known as c.3213G>C), located in coding exon 28 of the IKBKAP gene, results from a G to C substitution at nucleotide position 3213. The glutamic acid at codon 1071 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial dysautonomia Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at