Variant 22-18173093-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.104

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 -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 linkuse as main transcript	c.892-57G>A		intron_variant		ENST00000215794.8
USP18	XM_006724074.4 linkuse as main transcript	c.670-57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP18	ENST00000215794.8 linkuse as main transcript	c.892-57G>A	intron_variant		1	NM_017414.4	P1	Q9UMW8-1
USP18	ENST00000699060.1 linkuse as main transcript	c.724-57G>A	intron_variant
USP18	ENST00000699062.1 linkuse as main transcript	n.2129G>A	non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

115282

AN:

147482

Hom.:

45624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.729

Gnomad OTH

AF:

0.744

GnomAD4 exome

AF:

0.738

AC:

1062572

AN:

1439670

Hom.:

395640

AF XY:

0.736

AC XY:

526917

AN XY:

715708

show subpopulations

Gnomad4 AFR exome

AF:

0.902

Gnomad4 AMR exome

AF:

0.771

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.828

Gnomad4 SAS exome

AF:

0.704

Gnomad4 FIN exome

AF:

0.776

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.782

AC:

115382

AN:

147584

Hom.:

45669

Cov.:

AF XY:

0.782

AC XY:

56311

AN XY:

72024

show subpopulations

Gnomad4 AFR

AF:

0.901

Gnomad4 AMR

AF:

0.755

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.832

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.769

Gnomad4 NFE

AF:

0.729

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.766

Hom.:

6450

Asia WGS

AF:

0.744

AC:

2587

AN:

3476

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

DANN

Benign

0.75

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.

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