19-852104-C-A

Position:

• chr19-852104-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000590230.5(ELANE):​c.-120-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 596,156 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (1352 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2574 hom.)
• Consequence: ELANE ENST00000590230.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.130

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-852104-C-A is Benign according to our data. Variant chr19-852104-C-A is described in ClinVar as [Benign]. Clinvar id is 677093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELANE	ENST00000590230.5	c.-120-105C>A		intron_variant		5		ENSP00000466090	P1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13484 AN: 152132 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00777

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.0539 AC: 23918 AN: 443906 Hom.: 2574 AF XY: 0.0551 AC XY: 12849 AN XY: 233006

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.0899

Gnomad4 ASJ exome AF: 0.0140

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0342

Gnomad4 NFE exome AF: 0.00744

Gnomad4 OTH exome AF: 0.0551

GnomAD4 genome AF: 0.0888 AC: 13517 AN: 152250 Hom.: 1352 Cov.: 32 AF XY: 0.0923 AC XY: 6868 AN XY: 74448

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.0798

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0299 Hom.: 306

Bravo AF: 0.0982

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs740021; hg19: chr19-852104;