16-8894531-G-GC

Position:

• chr16-8894531-G-GC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003470.3(USP7):​c.3202+18_3202+19insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,465,380 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-8894531-G-GC is Benign according to our data. Variant chr16-8894531-G-GC is described in ClinVar as [Benign]. Clinvar id is 1971503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.3202+18_3202+19insG		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+18_3202+19insG		intron_variant		1	NM_003470.3	ENSP00000343535	P1

Frequencies

GnomAD3 genomes AF: 0.000581 AC: 36 AN: 61990 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00141

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000801

Gnomad OTH AF: 0.00249

GnomAD3 exomes AF: 0.000624 AC: 63 AN: 100894 Hom.: 0 AF XY: 0.000420 AC XY: 23 AN XY: 54764

Gnomad AFR exome AF: 0.000949

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000716

Gnomad SAS exome AF: 0.000296

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000483

Gnomad OTH exome AF: 0.00221

GnomAD4 exome AF: 0.000216 AC: 303 AN: 1403358 Hom.: 0 Cov.: 36 AF XY: 0.000196 AC XY: 137 AN XY: 697838

Gnomad4 AFR exome AF: 0.000307

Gnomad4 AMR exome AF: 0.000531

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000345

Gnomad4 SAS exome AF: 0.000120

Gnomad4 FIN exome AF: 0.0000397

Gnomad4 NFE exome AF: 0.000204

Gnomad4 OTH exome AF: 0.000451

GnomAD4 genome AF: 0.000580 AC: 36 AN: 62022 Hom.: 1 Cov.: 33 AF XY: 0.000426 AC XY: 13 AN XY: 30486

Gnomad4 AFR AF: 0.000316

Gnomad4 AMR AF: 0.000425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00141

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000802

Gnomad4 OTH AF: 0.00246

Bravo AF: 0.000249

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

Sep 24, 2023

- -

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: rs534626904; hg19: chr16-8988388;