chr22-18173093-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_017414.4(USP18):c.892-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,587,254 control chromosomes in the GnomAD database, including 441,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.78 ( 45669 hom., cov: 29)
Exomes 𝑓: 0.74 ( 395640 hom. )
Consequence
USP18
NM_017414.4 intron
NM_017414.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.104
Genes affected
USP18 (HGNC:12616): (ubiquitin specific peptidase 18) The protein encoded by this gene belongs to the ubiquitin-specific proteases (UBP) family of enzymes that cleave ubiquitin from ubiquitinated protein substrates. It is highly expressed in liver and thymus, and is localized to the nucleus. This protein efficiently cleaves only ISG15 (a ubiquitin-like protein) fusions, and deletion of this gene in mice results in a massive increase of ISG15 conjugates in tissues, indicating that this protein is a major ISG15-specific protease. Mice lacking this gene are also hypersensitive to interferon, suggesting a function of this protein in downregulating interferon responses, independent of its isopeptidase activity towards ISG15. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 22-18173093-G-A is Benign according to our data. Variant chr22-18173093-G-A is described in ClinVar as [Benign]. Clinvar id is 2628187.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP18 | NM_017414.4 | c.892-57G>A | intron_variant | ENST00000215794.8 | |||
USP18 | XM_006724074.4 | c.670-57G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP18 | ENST00000215794.8 | c.892-57G>A | intron_variant | 1 | NM_017414.4 | P1 | |||
USP18 | ENST00000699060.1 | c.724-57G>A | intron_variant | ||||||
USP18 | ENST00000699062.1 | n.2129G>A | non_coding_transcript_exon_variant | 1/3 |
Frequencies
GnomAD3 genomes AF: 0.782 AC: 115282AN: 147482Hom.: 45624 Cov.: 29
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GnomAD4 exome AF: 0.738 AC: 1062572AN: 1439670Hom.: 395640 AF XY: 0.736 AC XY: 526917AN XY: 715708
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GnomAD4 genome AF: 0.782 AC: 115382AN: 147584Hom.: 45669 Cov.: 29 AF XY: 0.782 AC XY: 56311AN XY: 72024
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at