rs30764

chr16-8954495-T-Cchr16-8954495-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003470.3(USP7):c.79+8712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,098 control chromosomes in the GnomAD database, including 5,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5717 hom., cov: 32)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP7	NM_003470.3	c.79+8712A>G		intron_variant		ENST00000344836.9
USP7	NM_001321858.2	c.-96+1813A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP7	ENST00000344836.9	c.79+8712A>G		intron_variant		1	NM_003470.3	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39994 AN: 151980 Hom.: 5715 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40004 AN: 152098 Hom.: 5717 Cov.: 32 AF XY: 0.263 AC XY: 19577 AN XY: 74336

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.262

Alfa AF: 0.282 Hom.: 1422

Bravo AF: 0.263

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.56

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: rs30764; hg19: chr16-9048352;