rs30764

Variant names:

• chr16-8954495-T-C
• rs30764
• NM_003470.3:c.79+8712A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-8954495-T-C
• chr16-8954495-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	NM_003470.3	MANE Select	c.79+8712A>G		intron	N/A	NP_003461.2
	USP7	NM_001321858.2		c.-96+1813A>G		intron	N/A	NP_001308787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	ENST00000344836.9	TSL:1 MANE Select	c.79+8712A>G		intron	N/A	ENSP00000343535.4
	USP7	ENST00000673704.1		c.184+20599A>G		intron	N/A	ENSP00000501290.1
	USP7	ENST00000923082.1		c.79+8712A>G		intron	N/A	ENSP00000593141.1

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

African (AFR) AF: 0.141 AC: 5839 AN: 41506

American (AMR) AF: 0.328 AC: 5012 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1407 AN: 5172

South Asian (SAS) AF: 0.341 AC: 1644 AN: 4818

European-Finnish (FIN) AF: 0.282 AC: 2977 AN: 10572

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21328 AN: 67970

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.285 Hom.: 2393

Bravo AF: 0.263

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.16
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: rs30764; hg19: chr16-9048352;