16-8894529-CG-C

Position:

• chr16-8894529-CG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000344836.9(USP7):​c.3202+20del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10222 hom., cov: 0)
  • Exomes 𝑓: 0.43 (115002 hom.)
• Consequence: USP7 ENST00000344836.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.21

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-8894529-CG-C is Benign according to our data. Variant chr16-8894529-CG-C is described in ClinVar as [Benign]. Clinvar id is 1283146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.3202+20del		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+20del		intron_variant		1	NM_003470.3	ENSP00000343535	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54592 AN: 150908 Hom.: 10213 Cov.: 0

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.429 AC: 90787 AN: 211410 Hom.: 17461 AF XY: 0.430 AC XY: 49418 AN XY: 114926

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.409

Gnomad FIN exome AF: 0.434

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.432 AC: 577303 AN: 1336284 Hom.: 115002 Cov.: 0 AF XY: 0.432 AC XY: 287011 AN XY: 665064

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.362 AC: 54642 AN: 151016 Hom.: 10222 Cov.: 0 AF XY: 0.360 AC XY: 26535 AN XY: 73716

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.376

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2021	- -

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: rs3214650; hg19: chr16-8988386;