19-855966-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001972.4(ELANE):c.606C>T(p.Ser202Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,613,142 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00058 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 7 hom. )
Consequence
ELANE
NM_001972.4 synonymous
NM_001972.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.42
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 19-855966-C-T is Benign according to our data. Variant chr19-855966-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.42 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000578 (88/152290) while in subpopulation EAS AF= 0.0137 (71/5180). AF 95% confidence interval is 0.0111. There are 3 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 88 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | c.606C>T | p.Ser202Ser | synonymous_variant | 5/5 | ENST00000263621.2 | NP_001963.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000263621.2 | c.606C>T | p.Ser202Ser | synonymous_variant | 5/5 | 1 | NM_001972.4 | ENSP00000263621.1 | ||
ELANE | ENST00000590230.5 | c.606C>T | p.Ser202Ser | synonymous_variant | 6/6 | 5 | ENSP00000466090.1 |
Frequencies
GnomAD3 genomes AF: 0.000578 AC: 88AN: 152172Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00105 AC: 261AN: 248642Hom.: 3 AF XY: 0.00116 AC XY: 157AN XY: 135128
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GnomAD4 exome AF: 0.000336 AC: 491AN: 1460852Hom.: 7 Cov.: 34 AF XY: 0.000392 AC XY: 285AN XY: 726730
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GnomAD4 genome AF: 0.000578 AC: 88AN: 152290Hom.: 3 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 25, 2016 | - - |
Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 21, 2023 | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 04, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at