rs17223045

Positions:

chr19-855587-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001972.4(ELANE):c.390C>T(p.Asn130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,600,284 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 130 hom., cov: 32)

Exomes 𝑓: 0.013 ( 242 hom. )

Consequence

ELANE
NM_001972.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.34

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-855587-C-T is Benign according to our data. Variant chr19-855587-C-T is described in ClinVar as [Benign]. Clinvar id is 258498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-855587-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELANE	NM_001972.4 linkuse as main transcript	c.390C>T	p.Asn130=	synonymous_variant	4/5	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.390C>T	p.Asn130=	synonymous_variant	4/5	1	NM_001972.4	ENSP00000263621	P1
ELANE	ENST00000590230.5 linkuse as main transcript	c.390C>T	p.Asn130=	synonymous_variant	5/6	5		ENSP00000466090	P1

Frequencies

GnomAD3 genomes

AF:

0.0276

AC:

4199

AN:

152226

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0149

AC:

3474

AN:

232666

Hom.:

AF XY:

0.0144

AC XY:

1846

AN XY:

127970

show subpopulations

Gnomad AFR exome

AF:

0.0720

Gnomad AMR exome

AF:

0.00960

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0207

Gnomad FIN exome

AF:

0.00376

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0127

AC:

18379

AN:

1447940

Hom.:

242

Cov.:

AF XY:

0.0129

AC XY:

9331

AN XY:

720890

show subpopulations

Gnomad4 AFR exome

AF:

0.0744

Gnomad4 AMR exome

AF:

0.00998

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.0151

GnomAD4 genome

AF:

0.0276

AC:

4210

AN:

152344

Hom.:

130

Cov.:

AF XY:

0.0275

AC XY:

2049

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0711

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0197

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0136

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 16, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.4

DANN

Benign

0.87

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