rs200599820
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001972.4(ELANE):c.456G>A(p.Leu152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,607,302 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L152L) has been classified as Likely benign.
Frequency
Consequence
NM_001972.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELANE | NM_001972.4 | c.456G>A | p.Leu152= | synonymous_variant | 4/5 | ENST00000263621.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELANE | ENST00000263621.2 | c.456G>A | p.Leu152= | synonymous_variant | 4/5 | 1 | NM_001972.4 | P1 | |
ELANE | ENST00000590230.5 | c.456G>A | p.Leu152= | synonymous_variant | 5/6 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000990 AC: 24AN: 242304Hom.: 0 AF XY: 0.000121 AC XY: 16AN XY: 132386
GnomAD4 exome AF: 0.0000447 AC: 65AN: 1455056Hom.: 2 Cov.: 32 AF XY: 0.0000483 AC XY: 35AN XY: 724146
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 26, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2017 | A variant of uncertain significance has been identified in the ELANE gene. The c.456 G>A (L152L) variant has been published previously in an individual with cyclic neutropenia (Germeshausen et al., 2013). The variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, this substitution occurs at a position that is conserved in mammals. However, the variant does not result in a change to the protein, and in silico analysis predicts this variant likely does not alter splicing. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Cyclical neutropenia;C1859966:Neutropenia, severe congenital, 1, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at