rs7226229

Variant names:

• chr17-21020764-C-T
• rs7226229
• NM_015276.2:c.418+349G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP22	NM_015276.2	c.418+349G>A		intron_variant	Intron 3 of 12	ENST00000261497.9	NP_056091.1
USP22	XM_005256575.3	c.103+349G>A		intron_variant	Intron 3 of 12		XP_005256632.1
USP22	XM_047435703.1	c.103+349G>A		intron_variant	Intron 2 of 11		XP_047291659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP22	ENST00000261497.9	c.418+349G>A		intron_variant	Intron 3 of 12	1	NM_015276.2	ENSP00000261497.4

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

African (AFR) AF: 0.631 AC: 26131 AN: 41436

American (AMR) AF: 0.708 AC: 10805 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2752 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2265 AN: 5154

South Asian (SAS) AF: 0.823 AC: 3958 AN: 4810

European-Finnish (FIN) AF: 0.792 AC: 8369 AN: 10570

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53840 AN: 67924

Other (OTH) AF: 0.737 AC: 1547 AN: 2098

Alfa AF: 0.732 Hom.: 12517

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7226229; hg19: chr17-20924077;