Variant rs773808780 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_001972.4(ELANE):c.338A>T(p.Asn113Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ELANE
NM_001972.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.49

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]

ELANE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a domain Peptidase S1 (size 217) in uniprot entity ELNE_HUMAN there are 55 pathogenic changes around while only 2 benign (96%) in NM_001972.4

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELANE	NM_001972.4 linkuse as main transcript	c.338A>T	p.Asn113Ile	missense_variant	3/5	ENST00000263621.2	NP_001963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELANE	ENST00000263621.2 linkuse as main transcript	c.338A>T	p.Asn113Ile	missense_variant	3/5	1	NM_001972.4	ENSP00000263621	P1
ELANE	ENST00000590230.5 linkuse as main transcript	c.338A>T	p.Asn113Ile	missense_variant	4/6	5		ENSP00000466090	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237154

Hom.:

AF XY:

0.00000770

AC XY:

AN XY:

129796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458658

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725486

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:

0.0000814

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000837

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.28

CADD

Benign

0.051

DANN

Benign

0.69

DEOGEN2

Pathogenic

0.81

D;D

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.38

.;T

M_CAP

Pathogenic

0.88

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.77

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.27

Sift

Benign

0.12

.;T

Sift4G

Benign

0.11

T;T

Polyphen

0.17

B;B

Vest4

0.29

MutPred

0.64

Loss of phosphorylation at Y109 (P = 0.1679);Loss of phosphorylation at Y109 (P = 0.1679);

MVP

0.78

MPC

0.73

ClinPred

0.35

GERP RS

-8.0

Varity_R

0.31

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over