19-851457-A-G

Variant names:

• chr19-851457-A-G
• rs7260160
• ENST00000590230.5:c.-121+423A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The ENST00000590230.5(ELANE):​c.-121+423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 129,764 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.0075 (1 hom., cov: 26)
• Consequence: ELANE ENST00000590230.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.23

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-851457-A-G is Benign according to our data. Variant chr19-851457-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3030858.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00748 (971/129764) while in subpopulation EAS AF= 0.0291 (101/3468). AF 95% confidence interval is 0.0254. There are 1 homozygotes in gnomad4. There are 507 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 971 AD gene.

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.-121+423A>G		intron_variant	Intron 1 of 5	5		ENSP00000466090.1

Frequencies

GnomAD3 genomes AF: 0.00748 AC: 970 AN: 129702 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.000586

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.00694

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000612

Gnomad OTH AF: 0.00554

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

GnomAD4 genome AF: 0.00748 AC: 971 AN: 129764 Hom.: 1 Cov.: 26 AF XY: 0.00806 AC XY: 507 AN XY: 62926

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.000586

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.00671

Gnomad4 FIN AF: 0.00227

Gnomad4 NFE AF: 0.000612

Gnomad4 OTH AF: 0.00551

Alfa AF: 0.0826 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ELANE-related disorder Benign:1

Jun 20, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.8
DANN	Benign	0.67

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: rs7260160; hg19: chr19-851457;