rs2007647

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000958526.1(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 ENST00000958526.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• neutropenia

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• cyclic hematopoiesis

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal dominant severe congenital neutropenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000958526.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELANE	ENST00000590230.5	TSL:5	c.-120-233G>A		intron	N/A	ENSP00000466090.1	P08246
	ELANE	ENST00000958526.1		c.-120-233G>A		intron	N/A	ENSP00000628585.1

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

African (AFR) AF: 0.134 AC: 5546 AN: 41518

American (AMR) AF: 0.155 AC: 2363 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3470

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5188

South Asian (SAS) AF: 0.180 AC: 871 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3185 AN: 10584

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15508 AN: 67972

Other (OTH) AF: 0.186 AC: 394 AN: 2114

Alfa AF: 0.209 Hom.: 430

Bravo AF: 0.176

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.88
PhyloP100		0.0040
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2007647; hg19: chr19-851976;