chr19-851976-G-A

Variant names:

• chr19-851976-G-A
• rs2007647
• ENST00000590230.5:c.-120-233G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000590230.5(ELANE):​c.-120-233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,168 control chromosomes in the GnomAD database, including 3,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3085 hom., cov: 32)
• Consequence: ELANE ENST00000590230.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-851976-G-A is Benign according to our data. Variant chr19-851976-G-A is described in ClinVar as [Benign]. Clinvar id is 667820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELANE	ENST00000590230.5	c.-120-233G>A		intron_variant	Intron 1 of 5	5		ENSP00000466090.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29026 AN: 152050 Hom.: 3087 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29035 AN: 152168 Hom.: 3085 Cov.: 32 AF XY: 0.191 AC XY: 14201 AN XY: 74394

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.186

Alfa AF: 0.209 Hom.: 430

Bravo AF: 0.176

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.86
CADD	Benign	4.7
DANN	Benign	0.88

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: rs2007647; hg19: chr19-851976;