16-8894529-CGGG-CG

Variant names:

• chr16-8894529-CGG-C
• rs3214650
• NM_003470.3:c.3202+19_3202+20delCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003470.3(USP7):​c.3202+19_3202+20delCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,488,068 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (9 hom., cov: 0)
  • Exomes 𝑓: 0.0033 (111 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.00
• Publications: 0 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, Illumina, ClinGen
• Hao-Fountain syndrome due to USP7 mutation

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-8894529-CGG-C is Benign according to our data. Variant chr16-8894529-CGG-C is described in ClinVar as Benign. ClinVar VariationId is 1666910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0563 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.3202+19_3202+20delCC		intron	N/A	NP_003461.2	Q93009-1
	USP7	NM_001286457.2		c.3154+19_3154+20delCC		intron	N/A	NP_001273386.2	Q93009-3
	USP7	NM_001321858.2		c.3028+19_3028+20delCC		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.3202+19_3202+20delCC		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000381886.8	TSL:1	c.3154+19_3154+20delCC		intron	N/A	ENSP00000371310.4	Q93009-3
	USP7	ENST00000673704.1		c.3307+19_3307+20delCC		intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 631 AN: 150996 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.00251

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00531

GnomAD2 exomes AF: 0.0107 AC: 2254 AN: 211410 AF XY: 0.00874

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.0431

Gnomad ASJ exome AF: 0.00253

Gnomad EAS exome AF: 0.0541

Gnomad FIN exome AF: 0.0000605

Gnomad NFE exome AF: 0.000278

Gnomad OTH exome AF: 0.00822

GnomAD4 exome AF: 0.00334 AC: 4465 AN: 1336964 Hom.: 111 AF XY: 0.00315 AC XY: 2093 AN XY: 665360

African (AFR) AF: 0.000627 AC: 20 AN: 31884

American (AMR) AF: 0.0402 AC: 1643 AN: 40892

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 68 AN: 24032

East Asian (EAS) AF: 0.0584 AC: 2059 AN: 35284

South Asian (SAS) AF: 0.00313 AC: 241 AN: 76934

European-Finnish (FIN) AF: 0.000109 AC: 5 AN: 45948

Middle Eastern (MID) AF: 0.00282 AC: 11 AN: 3902

European-Non Finnish (NFE) AF: 0.000228 AC: 233 AN: 1022674

Other (OTH) AF: 0.00334 AC: 185 AN: 55414

GnomAD4 genome AF: 0.00416 AC: 629 AN: 151104 Hom.: 9 Cov.: 0 AF XY: 0.00507 AC XY: 374 AN XY: 73764

African (AFR) AF: 0.00119 AC: 49 AN: 41136

American (AMR) AF: 0.0201 AC: 307 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3460

East Asian (EAS) AF: 0.0439 AC: 223 AN: 5084

South Asian (SAS) AF: 0.00251 AC: 12 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67748

Other (OTH) AF: 0.00525 AC: 11 AN: 2094

Alfa AF: 0.00182 Hom.: 1411

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.0
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: rs3214650; hg19: chr16-8988386;