XR_007067999.1:n.115+502G>A

Variant names:

• chr22-18148598-C-T
• rs9618216
• ENST00000896317.1:c.-178C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007067999.1(LOC124905076):​n.115+502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,176 control chromosomes in the GnomAD database, including 1,485 homozygotes. 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: 𝑓 0.13 (1485 hom., cov: 31)
• Consequence: LOC124905076 XR_007067999.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• pseudo-TORCH syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Illumina

LOC124905076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000896317.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP18	ENST00000896317.1		c.-178C>T		5_prime_UTR	Exon 1 of 11	ENSP00000566376.1
	USP18	ENST00000896318.1		c.-219C>T		upstream_gene	N/A	ENSP00000566377.1
	USP18	ENST00000896319.1		c.-536C>T		upstream_gene	N/A	ENSP00000566378.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19784 AN: 152060 Hom.: 1475 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19835 AN: 152176 Hom.: 1485 Cov.: 31 AF XY: 0.129 AC XY: 9596 AN XY: 74422

African (AFR) AF: 0.191 AC: 7910 AN: 41496

American (AMR) AF: 0.136 AC: 2081 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.131 AC: 679 AN: 5174

South Asian (SAS) AF: 0.149 AC: 720 AN: 4822

European-Finnish (FIN) AF: 0.0717 AC: 760 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6973 AN: 68016

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.113 Hom.: 3630

Bravo AF: 0.136

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.62
PhyloP100		-0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9618216; hg19: chr22-18631365;