rs17216649

Variant names:

• chr19-855966-C-A
• rs17216649
• NM_001972.4:c.606C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-855966-C-A
• chr19-855966-C-G
• chr19-855966-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.42
• Publications: 12 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001972.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELANE	NM_001972.4	MANE Select	c.606C>A	p.Ser202Ser	synonymous	Exon 5 of 5	NP_001963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELANE	ENST00000263621.2	TSL:1 MANE Select	c.606C>A	p.Ser202Ser	synonymous	Exon 5 of 5	ENSP00000263621.1
	ELANE	ENST00000590230.5	TSL:5	c.606C>A	p.Ser202Ser	synonymous	Exon 6 of 6	ENSP00000466090.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18008 AN: 152158 Hom.: 1547 Cov.: 32

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

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.: 34 AF XY: 0.159 AC XY: 115695 AN XY: 726710

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: 17 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

GnomAD4 genome AF: 0.118 AC: 18003 AN: 152276 Hom.: 1546 Cov.: 32 AF XY: 0.118 AC XY: 8820 AN XY: 74458

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: 4 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: 21 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11993 AN: 67984

Other (OTH) AF: 0.110 AC: 233 AN: 2116

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.10
DANN	Benign	0.67
PhyloP100		-1.4
Mutation Taster		=98/2	polymorphism (auto)

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: rs17216649; hg19: chr19-855966;