Variant 22-18157533-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.-106-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,186,556 control chromosomes in the GnomAD database, including 33,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 6048 hom., cov: 32)

Exomes 𝑓: 0.20 ( 27619 hom. )

Consequence

USP18
NM_017414.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.759

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=-0.96).

BP6

Variant 22-18157533-G-A is Benign according to our data. Variant chr22-18157533-G-A is described in ClinVar as [Benign]. Clinvar id is 2628193.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP18	NM_017414.4 linkuse as main transcript	c.-106-25G>A		intron_variant		ENST00000215794.8	NP_059110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP18	ENST00000215794.8 linkuse as main transcript	c.-106-25G>A		intron_variant		1	NM_017414.4	ENSP00000215794	P1	Q9UMW8-1
USP18	ENST00000699060.1 linkuse as main transcript	c.-106-25G>A		intron_variant				ENSP00000514107

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38332

AN:

151920

Hom.:

6012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.201

AC:

208380

AN:

1034518

Hom.:

27619

Cov.:

AF XY:

0.203

AC XY:

106014

AN XY:

522504

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.596

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.253

AC:

38425

AN:

152038

Hom.:

6048

Cov.:

AF XY:

0.254

AC XY:

18905

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.193

Hom.:

6809

Bravo

AF:

0.274

Asia WGS

AF:

0.463

AC:

1605

AN:

3478

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 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.36

DANN

Benign

0.89

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