19-852990-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001972.4(ELANE):āc.182C>Gā(p.Ala61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,446 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
ELANE
NM_001972.4 missense
NM_001972.4 missense
Scores
1
7
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.727
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a disulfide_bond (size 16) in uniprot entity ELNE_HUMAN there are 11 pathogenic changes around while only 0 benign (100%) in NM_001972.4
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | c.182C>G | p.Ala61Gly | missense_variant | 2/5 | ENST00000263621.2 | NP_001963.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000263621.2 | c.182C>G | p.Ala61Gly | missense_variant | 2/5 | 1 | NM_001972.4 | ENSP00000263621.1 | ||
ELANE | ENST00000590230.5 | c.182C>G | p.Ala61Gly | missense_variant | 3/6 | 5 | ENSP00000466090.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000210 AC: 3AN: 1427446Hom.: 0 Cov.: 34 AF XY: 0.00000282 AC XY: 2AN XY: 709058
GnomAD4 exome
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3
AN:
1427446
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34
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AC XY:
2
AN XY:
709058
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
2
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Uncertain
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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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