19-852205-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000958526.1(ELANE):c.-120-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,161,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

ELANE
ENST00000958526.1 splice_region, intron

Scores

Splicing: ADA: 0.00009145

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.71

Publications

0 publications found

Variant links:

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

ELANE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-852205-C-T is Benign according to our data. Variant chr19-852205-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255032.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000932 (142/152352) while in subpopulation AFR AF = 0.00339 (141/41586). AF 95% confidence interval is 0.00293. There are 0 homozygotes in GnomAd4. There are 66 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 142 AD gene.

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
	ELANE	NM_001972.4	MANE Select	c.-124C>T		upstream_gene	N/A	NP_001963.1	P08246

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELANE	ENST00000590230.5	TSL:5	c.-120-4C>T	splice_region intron	N/A	ENSP00000466090.1	P08246
ELANE	ENST00000958526.1		c.-120-4C>T	splice_region intron	N/A	ENSP00000628585.1
ELANE	ENST00000263621.2	TSL:1 MANE Select	c.-124C>T	upstream_gene	N/A	ENSP00000263621.1	P08246

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00342

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000773

AC:

AN:

1009544

Hom.:

Cov.:

AF XY:

0.0000745

AC XY:

AN XY:

509912

show subpopulations

African (AFR)

AF:

0.00290

AC:

AN:

24162

American (AMR)

AF:

0.000119

AC:

AN:

33520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21514

East Asian (EAS)

AF:

0.00

AC:

AN:

33934

South Asian (SAS)

AF:

0.00

AC:

AN:

70094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3354

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

744806

Other (OTH)

AF:

0.0000887

AC:

AN:

45078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152352

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00339

AC:

141

AN:

41586

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000994

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.2

(source)

DANN

Benign

0.91

PhyloP100

-1.7

PromoterAI

0.057

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0040

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over