NM_003470.3:c.3202+20delC

Variant names:

• chr16-8894529-CG-C
• rs3214650
• NM_003470.3:c.3202+20delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003470.3(USP7):​c.3202+20delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10222 hom., cov: 0)
  • Exomes 𝑓: 0.43 (115002 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.21
• 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 -16 ACMG points.

• BP6: Variant 16-8894529-CG-C is Benign according to our data. Variant chr16-8894529-CG-C is described in ClinVar as Benign. ClinVar VariationId is 1283146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 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+20delC		intron	N/A	NP_003461.2	Q93009-1
	USP7	NM_001286457.2		c.3154+20delC		intron	N/A	NP_001273386.2	Q93009-3
	USP7	NM_001321858.2		c.3028+20delC		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+20delC		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000381886.8	TSL:1	c.3154+20delC		intron	N/A	ENSP00000371310.4	Q93009-3
	USP7	ENST00000673704.1		c.3307+20delC		intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54592 AN: 150908 Hom.: 10213 Cov.: 0

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.429 AC: 90787 AN: 211410 AF XY: 0.430

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.263

Gnomad FIN exome AF: 0.434

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.432 AC: 577303 AN: 1336284 Hom.: 115002 Cov.: 0 AF XY: 0.432 AC XY: 287011 AN XY: 665064

African (AFR) AF: 0.268 AC: 8487 AN: 31694

American (AMR) AF: 0.451 AC: 18439 AN: 40854

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 10627 AN: 24028

East Asian (EAS) AF: 0.263 AC: 9276 AN: 35282

South Asian (SAS) AF: 0.390 AC: 30029 AN: 76920

European-Finnish (FIN) AF: 0.412 AC: 18896 AN: 45910

Middle Eastern (MID) AF: 0.422 AC: 1647 AN: 3902

European-Non Finnish (NFE) AF: 0.447 AC: 456868 AN: 1022318

Other (OTH) AF: 0.416 AC: 23034 AN: 55376

GnomAD4 genome AF: 0.362 AC: 54642 AN: 151016 Hom.: 10222 Cov.: 0 AF XY: 0.360 AC XY: 26535 AN XY: 73716

African (AFR) AF: 0.267 AC: 10968 AN: 41114

American (AMR) AF: 0.425 AC: 6473 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1397 AN: 3458

East Asian (EAS) AF: 0.219 AC: 1110 AN: 5078

South Asian (SAS) AF: 0.366 AC: 1746 AN: 4770

European-Finnish (FIN) AF: 0.376 AC: 3895 AN: 10362

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27805 AN: 67718

Other (OTH) AF: 0.376 AC: 787 AN: 2092

Alfa AF: 0.362 Hom.: 1411

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.2
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;