chr16-8897333-G-A

Variant names:

• chr16-8897333-G-A
• rs1529916
• NM_003470.3:c.2719-234C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• Hao-Fountain syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Illumina
• Hao-Fountain syndrome due to USP7 mutation

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003470.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	NM_003470.3	MANE Select	c.2719-234C>T		intron	N/A	NP_003461.2
	USP7	NM_001286457.2		c.2671-234C>T		intron	N/A	NP_001273386.2
	USP7	NM_001321858.2		c.2545-234C>T		intron	N/A	NP_001308787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	ENST00000344836.9	TSL:1 MANE Select	c.2719-234C>T		intron	N/A	ENSP00000343535.4
	USP7	ENST00000381886.8	TSL:1	c.2671-234C>T		intron	N/A	ENSP00000371310.4
	USP7	ENST00000673704.1		c.2824-234C>T		intron	N/A	ENSP00000501290.1

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

African (AFR) AF: 0.170 AC: 1704 AN: 10020

American (AMR) AF: 0.296 AC: 3406 AN: 11524

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 3042 AN: 10182

East Asian (EAS) AF: 0.247 AC: 5721 AN: 23198

South Asian (SAS) AF: 0.312 AC: 9257 AN: 29642

European-Finnish (FIN) AF: 0.274 AC: 6180 AN: 22596

Middle Eastern (MID) AF: 0.286 AC: 425 AN: 1488

European-Non Finnish (NFE) AF: 0.307 AC: 62639 AN: 204210

Other (OTH) AF: 0.283 AC: 5476 AN: 19316

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

African (AFR) AF: 0.169 AC: 7007 AN: 41416

American (AMR) AF: 0.277 AC: 4217 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3466

East Asian (EAS) AF: 0.212 AC: 1087 AN: 5132

South Asian (SAS) AF: 0.336 AC: 1614 AN: 4806

European-Finnish (FIN) AF: 0.271 AC: 2860 AN: 10538

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20818 AN: 67918

Other (OTH) AF: 0.250 AC: 525 AN: 2100

Alfa AF: 0.245 Hom.: 1851

Bravo AF: 0.257

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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