rs5992185

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017414.4(USP18):​c.-107+989A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,846 control chromosomes in the GnomAD database, including 13,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13125 hom., cov: 32)

Consequence

USP18
NM_017414.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP18NM_017414.4 linkuse as main transcriptc.-107+989A>C intron_variant ENST00000215794.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP18ENST00000215794.8 linkuse as main transcriptc.-107+989A>C intron_variant 1 NM_017414.4 P1Q9UMW8-1
USP18ENST00000699060.1 linkuse as main transcriptc.-107+989A>C intron_variant

Frequencies

GnomAD3 genomes
AF:
0.398
AC:
60347
AN:
151728
Hom.:
13105
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.566
Gnomad AMI
AF:
0.577
Gnomad AMR
AF:
0.324
Gnomad ASJ
AF:
0.376
Gnomad EAS
AF:
0.0545
Gnomad SAS
AF:
0.232
Gnomad FIN
AF:
0.348
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.358
Gnomad OTH
AF:
0.369
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.398
AC:
60418
AN:
151846
Hom.:
13125
Cov.:
32
AF XY:
0.393
AC XY:
29140
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.566
Gnomad4 AMR
AF:
0.324
Gnomad4 ASJ
AF:
0.376
Gnomad4 EAS
AF:
0.0544
Gnomad4 SAS
AF:
0.233
Gnomad4 FIN
AF:
0.348
Gnomad4 NFE
AF:
0.358
Gnomad4 OTH
AF:
0.365
Alfa
AF:
0.357
Hom.:
20513
Bravo
AF:
0.402
Asia WGS
AF:
0.163
AC:
571
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
1.9
DANN
Benign
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5992185; hg19: chr22-18633978; API