Genetic Variant USP7:c.3202+18_3202+19insG (chr16-8894531-G-GC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003470.3(USP7):c.3202+18_3202+19insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,465,380 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

USP7
NM_003470.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.90

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 16-8894531-G-GC is Benign according to our data. Variant chr16-8894531-G-GC is described in ClinVar as Benign. ClinVar VariationId is 1971503.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 36 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+18_3202+19insG	intron	N/A	NP_003461.2	Q93009-1
USP7	NM_001286457.2		c.3154+18_3154+19insG	intron	N/A	NP_001273386.2	Q93009-3
USP7	NM_001321858.2		c.3028+18_3028+19insG	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+18_3202+19insG	intron	N/A	ENSP00000343535.4	Q93009-1
USP7	ENST00000381886.8	TSL:1	c.3154+18_3154+19insG	intron	N/A	ENSP00000371310.4	Q93009-3
USP7	ENST00000673704.1		c.3307+18_3307+19insG	intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes

AF:

0.000581

AC:

AN:

61990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00141

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000801

Gnomad OTH

AF:

0.00249

GnomAD2 exomes

AF:

0.000624

AC:

AN:

100894

AF XY:

0.000420

show subpopulations

Gnomad AFR exome

AF:

0.000949

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000716

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000483

Gnomad OTH exome

AF:

0.00221

GnomAD4 exome

AF:

0.000216

AC:

303

AN:

1403358

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

137

AN XY:

697838

show subpopulations

African (AFR)

AF:

0.000307

AC:

AN:

32558

American (AMR)

AF:

0.000531

AC:

AN:

39520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24888

East Asian (EAS)

AF:

0.000345

AC:

AN:

34820

South Asian (SAS)

AF:

0.000120

AC:

AN:

83062

European-Finnish (FIN)

AF:

0.0000397

AC:

AN:

50376

Middle Eastern (MID)

AF:

0.000495

AC:

AN:

4038

European-Non Finnish (NFE)

AF:

0.000204

AC:

220

AN:

1076426

Other (OTH)

AF:

0.000451

AC:

AN:

57670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000580

AC:

AN:

62022

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

AN XY:

30486

show subpopulations

African (AFR)

AF:

0.000316

AC:

AN:

22180

American (AMR)

AF:

0.000425

AC:

AN:

4708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1230

East Asian (EAS)

AF:

0.00141

AC:

AN:

2838

South Asian (SAS)

AF:

0.00103

AC:

AN:

1938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000802

AC:

AN:

23704

Other (OTH)

AF:

0.00246

AC:

AN:

814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000249

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over