rs7226229

Positions:

• chr17-21020764-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015276.2(USP22):​c.418+349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 151,936 control chromosomes in the GnomAD database, including 40,948 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 0.73 (40948 hom., cov: 30)
• Consequence: USP22 NM_015276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

USP22 (HGNC:12621): (ubiquitin specific peptidase 22) Enables enzyme binding activity; nuclear receptor coactivator activity; and thiol-dependent deubiquitinase. Contributes to H4 histone acetyltransferase activity. Involved in positive regulation of mitotic cell cycle; positive regulation of transcription, DNA-templated; and protein modification by small protein conjugation or removal. Part of SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP22	NM_015276.2	c.418+349G>A		intron_variant		ENST00000261497.9
USP22	XM_005256575.3	c.103+349G>A		intron_variant
USP22	XM_047435703.1	c.103+349G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP22	ENST00000261497.9	c.418+349G>A		intron_variant		1	NM_015276.2	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110571 AN: 151814 Hom.: 40922 Cov.: 30

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.728 AC: 110655 AN: 151936 Hom.: 40948 Cov.: 30 AF XY: 0.727 AC XY: 53965 AN XY: 74262

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.737

Alfa AF: 0.743 Hom.: 5594

Bravo AF: 0.712

Asia WGS AF: 0.622 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs7226229; hg19: chr17-20924077;