Genetic Variant USP7:c.3202+20C>G (chr16-8894530-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003470.3(USP7):c.3202+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000090 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

USP7
NM_003470.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.21

Publications

0 publications found

Variant links:

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

USP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS2

High AC in GnomAdExome4 at 15 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP7	NM_003470.3	MANE Select	c.3202+20C>G	intron	N/A	NP_003461.2	Q93009-1
USP7	NM_001286457.2		c.3154+20C>G	intron	N/A	NP_001273386.2	Q93009-3
USP7	NM_001321858.2		c.3028+20C>G	intron	N/A	NP_001308787.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP7	ENST00000344836.9	TSL:1 MANE Select	c.3202+20C>G	intron	N/A	ENSP00000343535.4	Q93009-1
USP7	ENST00000381886.8	TSL:1	c.3154+20C>G	intron	N/A	ENSP00000371310.4	Q93009-3
USP7	ENST00000673704.1		c.3307+20C>G	intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes

AF:

0.0000904

AC:

AN:

11058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00806

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000334

AC:

AN:

119738

AF XY:

0.0000309

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000292

AC:

AN:

513210

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

256034

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

16358

American (AMR)

AF:

0.00

AC:

AN:

12552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8772

East Asian (EAS)

AF:

0.00

AC:

AN:

20192

South Asian (SAS)

AF:

0.00

AC:

AN:

35856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1470

European-Non Finnish (NFE)

AF:

0.0000319

AC:

AN:

375740

Other (OTH)

AF:

0.0000451

AC:

AN:

22172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000904

AC:

AN:

11058

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10620

American (AMR)

AF:

0.00

AC:

AN:

188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00806

AC:

AN:

124

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0020

(source)

DANN

Benign

0.14

PhyloP100

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=38/62

disease causing (long InDel)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over