rs17216614
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000590230.5(ELANE):c.-41C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,596,522 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 27 hom. )
Consequence
ELANE
ENST00000590230.5 5_prime_UTR
ENST00000590230.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.17
Genes affected
ELANE (HGNC:3309): (elastase, neutrophil expressed) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode structurally similar proteins. The encoded preproprotein is proteolytically processed to generate the active protease. Following activation, this protease hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix. The enzyme may play a role in degenerative and inflammatory diseases through proteolysis of collagen-IV and elastin. This protein also degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with cyclic neutropenia and severe congenital neutropenia (SCN). This gene is present in a gene cluster on chromosome 19. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 19-852288-C-A is Benign according to our data. Variant chr19-852288-C-A is described in ClinVar as [Benign]. Clinvar id is 137203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1616/152262) while in subpopulation AFR AF= 0.0355 (1473/41546). AF 95% confidence interval is 0.0339. There are 32 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1616 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | upstream_gene_variant | ENST00000263621.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000590230.5 | c.-41C>A | 5_prime_UTR_variant | 2/6 | 5 | P1 | |||
ELANE | ENST00000263621.2 | upstream_gene_variant | 1 | NM_001972.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0106 AC: 1611AN: 152144Hom.: 32 Cov.: 32
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GnomAD3 exomes AF: 0.00269 AC: 601AN: 223656Hom.: 11 AF XY: 0.00211 AC XY: 259AN XY: 122932
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GnomAD4 exome AF: 0.00110 AC: 1585AN: 1444260Hom.: 27 Cov.: 31 AF XY: 0.000970 AC XY: 697AN XY: 718638
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GnomAD4 genome ? AF: 0.0106 AC: 1616AN: 152262Hom.: 32 Cov.: 32 AF XY: 0.00991 AC XY: 738AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 27, 2023 | - - |
Computational scores
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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