rs1529916

Positions:

• chr16-8897333-G-A
• chr16-8897333-G-T

Variant summary

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

The NM_003470.3(USP7):​c.2719-234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 484,000 control chromosomes in the GnomAD database, including 20,159 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 (5414 hom., cov: 30)
  • Exomes 𝑓: 0.29 (14745 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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]

USP7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP7	NM_003470.3	c.2719-234C>T		intron_variant		ENST00000344836.9	NP_003461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP7	ENST00000344836.9	c.2719-234C>T		intron_variant		1	NM_003470.3	ENSP00000343535.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39428 AN: 151706 Hom.: 5413 Cov.: 30

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.295 AC: 97850 AN: 332176 Hom.: 14745 AF XY: 0.298 AC XY: 51960 AN XY: 174612

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.260 AC: 39441 AN: 151824 Hom.: 5414 Cov.: 30 AF XY: 0.259 AC XY: 19192 AN XY: 74180

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.250

Alfa AF: 0.268 Hom.: 758

Bravo AF: 0.257

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.43

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: rs1529916; hg19: chr16-8991190; COSMIC: COSV61217758; COSMIC: COSV61217758;