22-18167155-A-C

Variant names:

• chr22-18167155-A-C
• NM_017414.4:c.401-100A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017414.4(USP18):​c.401-100A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000635 in 1,259,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: USP18 NM_017414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP18	NM_017414.4	c.401-100A>C		intron_variant	Intron 4 of 10	ENST00000215794.8	NP_059110.2
USP18	XM_006724074.4	c.179-100A>C		intron_variant	Intron 3 of 9		XP_006724137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP18	ENST00000215794.8	c.401-100A>C		intron_variant	Intron 4 of 10	1	NM_017414.4	ENSP00000215794.7
USP18	ENST00000699060.1	c.401-100A>C		intron_variant	Intron 4 of 9			ENSP00000514107.1
USP18	ENST00000699061.1	n.147-100A>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000635 AC: 8 AN: 1259940 Hom.: 0 AF XY: 0.00000639 AC XY: 4 AN XY: 625770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18649922;