rs202204133
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001972.4(ELANE):c.378G>A(p.Ser126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 1,599,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
ELANE
NM_001972.4 synonymous
NM_001972.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.67
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 19-855575-G-A is Benign according to our data. Variant chr19-855575-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 535839.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.67 with no splicing effect.
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | c.378G>A | p.Ser126= | synonymous_variant | 4/5 | ENST00000263621.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000263621.2 | c.378G>A | p.Ser126= | synonymous_variant | 4/5 | 1 | NM_001972.4 | P1 | |
ELANE | ENST00000590230.5 | c.378G>A | p.Ser126= | synonymous_variant | 5/6 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000173 AC: 4AN: 231310Hom.: 0 AF XY: 0.0000235 AC XY: 3AN XY: 127404
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GnomAD4 exome AF: 0.0000214 AC: 31AN: 1447236Hom.: 0 Cov.: 32 AF XY: 0.0000180 AC XY: 13AN XY: 720534
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74420
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at