chr16-8894533-G-GT

Position:

• chr16-8894533-G-GT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_003470.3(USP7):​c.3202+16_3202+17insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,608,852 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.08

Genes affected

USP7 (HGNC:12630): (ubiquitin specific peptidase 7) The protein encoded by this gene belongs to the peptidase C19 family, which includes ubiquitinyl hydrolases. This protein deubiquitinates target proteins such as p53 (a tumor suppressor protein) and WASH (essential for endosomal protein recycling), and regulates their activities by counteracting the opposing ubiquitin ligase activity of proteins such as HDM2 and TRIM27, involved in the respective process. Mutations in this gene have been implicated in a neurodevelopmental disorder. [provided by RefSeq, Mar 2016]

USP7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 16-8894533-G-GT is Benign according to our data. Variant chr16-8894533-G-GT is described in ClinVar as [Benign]. Clinvar id is 1971125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.3202+16_3202+17insA		intron_variant		ENST00000344836.9	NP_003461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP7	ENST00000344836.9	c.3202+16_3202+17insA		intron_variant		1	NM_003470.3	ENSP00000343535.4

Frequencies

GnomAD3 genomes AF: 0.000916 AC: 139 AN: 151810 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000663

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00106 AC: 262 AN: 247586 Hom.: 3 AF XY: 0.00107 AC XY: 144 AN XY: 134374

Gnomad AFR exome AF: 0.000382

Gnomad AMR exome AF: 0.000704

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.000328

Gnomad FIN exome AF: 0.000386

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00135 AC: 1974 AN: 1456924 Hom.: 6 Cov.: 37 AF XY: 0.00137 AC XY: 990 AN XY: 724948

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.000630

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000465

Gnomad4 FIN exome AF: 0.000706

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.000915 AC: 139 AN: 151928 Hom.: 0 Cov.: 33 AF XY: 0.000916 AC XY: 68 AN XY: 74248

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000663

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000392 Hom.: 0

Bravo AF: 0.000979

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	USP7: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

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: rs543861049; hg19: chr16-8988390;