ENST00000590230:c.-91C>G

Variant names:

• chr19-852238-C-G
• rs370728101
• ENST00000590230.5:c.-91C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000590230.5(ELANE):​c.-91C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,489,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (1 hom.)
• Consequence: ELANE ENST00000590230.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.9).
• BP6: Variant 19-852238-C-G is Benign according to our data. Variant chr19-852238-C-G is described in ClinVar as Benign. ClinVar VariationId is 1243625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000578 (88/152220) while in subpopulation AMR AF = 0.00216 (33/15282). AF 95% confidence interval is 0.00158. There are 1 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 88 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590230.5. 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
	ELANE	NM_001972.4	MANE Select	c.-91C>G		upstream_gene	N/A	NP_001963.1	P08246

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELANE	ENST00000590230.5	TSL:5	c.-91C>G		5_prime_UTR	Exon 2 of 6	ENSP00000466090.1	P08246
	ELANE	ENST00000958526.1		c.-91C>G		5_prime_UTR	Exon 2 of 6	ENSP00000628585.1
	ELANE	ENST00000263621.2	TSL:1 MANE Select	c.-91C>G		upstream_gene	N/A	ENSP00000263621.1	P08246

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 152102 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000536 AC: 716 AN: 1337000 Hom.: 1 Cov.: 23 AF XY: 0.000519 AC XY: 345 AN XY: 664534

African (AFR) AF: 0.0000648 AC: 2 AN: 30860

American (AMR) AF: 0.00125 AC: 47 AN: 37518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24844

East Asian (EAS) AF: 0.00 AC: 0 AN: 36202

South Asian (SAS) AF: 0.000275 AC: 22 AN: 80044

European-Finnish (FIN) AF: 0.0000570 AC: 2 AN: 35108

Middle Eastern (MID) AF: 0.00142 AC: 6 AN: 4240

European-Non Finnish (NFE) AF: 0.000595 AC: 614 AN: 1031970

Other (OTH) AF: 0.000409 AC: 23 AN: 56214

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152220 Hom.: 1 Cov.: 32 AF XY: 0.000444 AC XY: 33 AN XY: 74402

African (AFR) AF: 0.000193 AC: 8 AN: 41550

American (AMR) AF: 0.00216 AC: 33 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68008

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000530 Hom.: 0

Bravo AF: 0.000975

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	0.34
DANN	Benign	0.58
PhyloP100		-1.7
PromoterAI		0.057	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs370728101; hg19: chr19-852238;