16-8894534-G-GC

Position:

• chr16-8894534-G-GC

Variant summary

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

The ENST00000344836.9(USP7):​c.3202+15_3202+16insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,609,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: USP7 ENST00000344836.9 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476

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 16-8894534-G-GC is Benign according to our data. Variant chr16-8894534-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 1972844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.3202+15_3202+16insG		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+15_3202+16insG		intron_variant		1	NM_003470.3	ENSP00000343535	P1

Frequencies

GnomAD3 genomes AF: 0.000350 AC: 53 AN: 151320 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000517

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000271 AC: 67 AN: 247238 Hom.: 0 AF XY: 0.000283 AC XY: 38 AN XY: 134130

Gnomad AFR exome AF: 0.0000635

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad SAS exome AF: 0.000394

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000464

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000543 AC: 792 AN: 1458010 Hom.: 0 Cov.: 36 AF XY: 0.000491 AC XY: 356 AN XY: 725462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000675

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000632

Gnomad4 OTH exome AF: 0.000731

GnomAD4 genome AF: 0.000350 AC: 53 AN: 151440 Hom.: 0 Cov.: 33 AF XY: 0.000257 AC XY: 19 AN XY: 74014

Gnomad4 AFR AF: 0.000290

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000518

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000728 Hom.: 0

Bravo AF: 0.000298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 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: rs778620228; hg19: chr16-8988391;