Variant 22-18160233-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_017414.4(USP18):c.219C>T(p.Phe73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

USP18
NM_017414.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0100

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]

USP18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 22-18160233-C-T is Benign according to our data. Variant chr22-18160233-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 723623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP18	NM_017414.4 linkuse as main transcript	c.219C>T	p.Phe73=	synonymous_variant	3/11	ENST00000215794.8
USP18	XM_006724074.4 linkuse as main transcript	c.-4C>T		5_prime_UTR_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP18	ENST00000215794.8 linkuse as main transcript	c.219C>T	p.Phe73=	synonymous_variant	3/11	1	NM_017414.4	P1	Q9UMW8-1
USP18	ENST00000699060.1 linkuse as main transcript	c.219C>T	p.Phe73=	synonymous_variant	3/10

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

132

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00137

AC:

344

AN:

251494

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000980

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00105

AC:

1532

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000997

AC XY:

725

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00429

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000867

AC:

132

AN:

152306

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000574

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	USP18: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.6

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over