rs140642538
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_001972.4(ELANE):c.556G>A(p.Val186Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,609,452 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V186V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001972.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | c.556G>A | p.Val186Ile | missense_variant | 4/5 | ENST00000263621.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000263621.2 | c.556G>A | p.Val186Ile | missense_variant | 4/5 | 1 | NM_001972.4 | P1 | |
ELANE | ENST00000590230.5 | c.556G>A | p.Val186Ile | missense_variant | 5/6 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000446 AC: 11AN: 246452Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134348
GnomAD4 exome AF: 0.0000350 AC: 51AN: 1457218Hom.: 0 Cov.: 32 AF XY: 0.0000345 AC XY: 25AN XY: 725038
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 13, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 186 of the ELANE protein (p.Val186Ile). This variant is present in population databases (rs140642538, gnomAD 0.009%). This missense change has been observed in individual(s) with severe congenital neutropenia (PMID: 19775295, 31321910). This variant is also known as V157I. ClinVar contains an entry for this variant (Variation ID: 265118). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2023 | Identified in patients with severe congenital neutropenia in published literature (Xia et al., 2009; Makaryan et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as p.(V157I); This variant is associated with the following publications: (PMID: 25427142, 31321910, 34426522, 19775295) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at