16-8894529-C-CGG

Position:

• chr16-8894529-C-CGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000344836.9(USP7):​c.3202+20_3202+21insCC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (2 hom.)
• Consequence: USP7 ENST00000344836.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 16-8894529-C-CGG is Benign according to our data. Variant chr16-8894529-C-CGG is described in ClinVar as [Benign]. Clinvar id is 1971378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00297 (449/151060) while in subpopulation EAS AF= 0.0191 (97/5082). AF 95% confidence interval is 0.016. There are 2 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 449 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.3202+20_3202+21insCC		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+20_3202+21insCC		intron_variant		1	NM_003470.3	ENSP00000343535	P1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 450 AN: 150952 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00296

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.00691

Gnomad FIN AF: 0.000772

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.00685 AC: 1448 AN: 211410 Hom.: 1 AF XY: 0.00671 AC XY: 771 AN XY: 114926

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.0316

Gnomad SAS exome AF: 0.00854

Gnomad FIN exome AF: 0.00387

Gnomad NFE exome AF: 0.00481

Gnomad OTH exome AF: 0.00420

GnomAD4 exome AF: 0.00574 AC: 7444 AN: 1296800 Hom.: 2 Cov.: 0 AF XY: 0.00577 AC XY: 3727 AN XY: 645542

Gnomad4 AFR exome AF: 0.00287

Gnomad4 AMR exome AF: 0.00441

Gnomad4 ASJ exome AF: 0.00414

Gnomad4 EAS exome AF: 0.0230

Gnomad4 SAS exome AF: 0.00965

Gnomad4 FIN exome AF: 0.00731

Gnomad4 NFE exome AF: 0.00495

Gnomad4 OTH exome AF: 0.00612

GnomAD4 genome AF: 0.00297 AC: 449 AN: 151060 Hom.: 2 Cov.: 0 AF XY: 0.00293 AC XY: 216 AN XY: 73732

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00318

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.00671

Gnomad4 FIN AF: 0.000772

Gnomad4 NFE AF: 0.00229

Gnomad4 OTH AF: 0.00239

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;