NM_001972.4:c.606C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001972.4(ELANE):c.606C>A(p.Ser202Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,084 control chromosomes in the GnomAD database, including 23,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S202S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1546 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22367 hom. )

Consequence

ELANE
NM_001972.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.42

Publications

12 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: Labcorp Genetics (formerly Invitae), Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 19-855966-C-A is Benign according to our data. Variant chr19-855966-C-A is described in ClinVar as Benign. ClinVar VariationId is 137199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELANE	NM_001972.4 link	c.606C>A	p.Ser202Ser	synonymous_variant	Exon 5 of 5	ENST00000263621.2	NP_001963.1	P08246

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELANE	ENST00000263621.2 link	c.606C>A	p.Ser202Ser	synonymous_variant	Exon 5 of 5	1	NM_001972.4	ENSP00000263621.1		P08246
ELANE	ENST00000590230.5 link	c.606C>A	p.Ser202Ser	synonymous_variant	Exon 6 of 6	5		ENSP00000466090.1		P08246

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

18008

AN:

152158

Hom.:

1547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.111

GnomAD2 exomes

AF:

0.122

AC:

30214

AN:

248642

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.0551

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.163

AC:

238797

AN:

1460808

Hom.:

22367

Cov.:

AF XY:

0.159

AC XY:

115695

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.0234

AC:

785

AN:

33480

American (AMR)

AF:

0.0584

AC:

2613

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3302

AN:

26136

East Asian (EAS)

AF:

0.000428

AC:

AN:

39700

South Asian (SAS)

AF:

0.0369

AC:

3186

AN:

86258

European-Finnish (FIN)

AF:

0.252

AC:

13205

AN:

52394

Middle Eastern (MID)

AF:

0.0590

AC:

340

AN:

5762

European-Non Finnish (NFE)

AF:

0.186

AC:

206592

AN:

1111972

Other (OTH)

AF:

0.145

AC:

8757

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

12768

25537

38305

51074

63842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7108

14216

21324

28432

35540

<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:

0.118

AC:

18003

AN:

152276

Hom.:

1546

Cov.:

AF XY:

0.118

AC XY:

8820

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0296

AC:

1229

AN:

41584

American (AMR)

AF:

0.0765

AC:

1171

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0396

AC:

191

AN:

4824

European-Finnish (FIN)

AF:

0.252

AC:

2675

AN:

10600

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11993

AN:

67984

Other (OTH)

AF:

0.110

AC:

233

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

810

1620

2430

3240

4050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.126

Hom.:

662

Bravo

AF:

0.104

EpiCase

AF:

0.166

EpiControl

AF:

0.162

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.10

(source)

DANN

Benign

0.67

PhyloP100

-1.4

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over