19-852990-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001972.4(ELANE):ā€‹c.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

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.727
Variant links:
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]

Genome browser will be placed here

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
ELANENM_001972.4 linkuse as main transcriptc.182C>G p.Ala61Gly missense_variant 2/5 ENST00000263621.2 NP_001963.1 P08246

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELANEENST00000263621.2 linkuse as main transcriptc.182C>G p.Ala61Gly missense_variant 2/51 NM_001972.4 ENSP00000263621.1 P08246
ELANEENST00000590230.5 linkuse as main transcriptc.182C>G p.Ala61Gly missense_variant 3/65 ENSP00000466090.1 P08246

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1427446
Hom.:
0
Cov.:
34
AF XY:
0.00000282
AC XY:
2
AN XY:
709058
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000169
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;D
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.082
N
LIST_S2
Benign
0.70
.;T
M_CAP
Pathogenic
0.47
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
0.29
N;N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.94
.;N
REVEL
Uncertain
0.32
Sift
Benign
0.13
.;T
Sift4G
Benign
0.13
T;T
Polyphen
0.96
D;D
Vest4
0.42
MutPred
0.64
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.81
MPC
1.2
ClinPred
0.30
T
GERP RS
3.2
Varity_R
0.55
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs137854447; hg19: chr19-852990; API