16-8894529-C-CG

Position:

• chr16-8894529-C-CG

Variant summary

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

The NM_003470.3(USP7):​c.3202+20_3202+21insC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17865 hom., cov: 0)
  • Exomes 𝑓: 0.46 (99961 hom.)
• Consequence: USP7 NM_003470.3 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-C-CG is Benign according to our data. Variant chr16-8894529-C-CG is described in ClinVar as [Benign]. Clinvar id is 1637214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.462 AC: 69583 AN: 150752 Hom.: 17868 Cov.: 0

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.459

GnomAD3 exomes AF: 0.442 AC: 93393 AN: 211410 Hom.: 13694 AF XY: 0.449 AC XY: 51644 AN XY: 114926

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.569

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.505

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.463 AC: 616975 AN: 1332954 Hom.: 99961 Cov.: 0 AF XY: 0.465 AC XY: 308167 AN XY: 663390

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.461 AC: 69601 AN: 150860 Hom.: 17865 Cov.: 0 AF XY: 0.467 AC XY: 34411 AN XY: 73614

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.461

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hao-Fountain syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 25, 2022

- -

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;