Variant chr22-18160167-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017414.4(USP18):c.158-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,613,882 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 3 hom. )

Consequence

USP18
NM_017414.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0009933

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-18160167-T-G is Benign according to our data. Variant chr22-18160167-T-G is described in ClinVar as [Benign]. Clinvar id is 785677.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP18	NM_017414.4 linkuse as main transcript	c.158-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000215794.8
USP18	XM_006724074.4 linkuse as main transcript	c.-65-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP18	ENST00000215794.8 linkuse as main transcript	c.158-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_017414.4	P1	Q9UMW8-1
USP18	ENST00000699060.1 linkuse as main transcript	c.158-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

494

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.000756

AC:

190

AN:

251478

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000322

AC:

470

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00328

AC:

499

AN:

152254

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.00331

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.6

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00099

dbscSNV1_RF

Benign

0.11

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