rs780907194

Variant names:

• chr16-8894532-G-A
• rs780907194
• NM_003470.3:c.3202+18C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-8894532-G-A
• chr16-8894532-G-C
• chr16-8894532-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003470.3(USP7):​c.3202+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 1,606,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-8894532-G-A is Benign according to our data. Variant chr16-8894532-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3697407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	NM_003470.3	MANE Select	c.3202+18C>T		intron	N/A	NP_003461.2	Q93009-1
	USP7	NM_001286457.2		c.3154+18C>T		intron	N/A	NP_001273386.2	Q93009-3
	USP7	NM_001321858.2		c.3028+18C>T		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+18C>T		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000381886.8	TSL:1	c.3154+18C>T		intron	N/A	ENSP00000371310.4	Q93009-3
	USP7	ENST00000673704.1		c.3307+18C>T		intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150478 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 241736 AF XY: 0.0000152

Gnomad AFR exome AF: 0.000128

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1456256 Hom.: 0 Cov.: 36 AF XY: 0.00000690 AC XY: 5 AN XY: 724572

African (AFR) AF: 0.000211 AC: 7 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4204

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110246

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150478 Hom.: 0 Cov.: 33 AF XY: 0.0000273 AC XY: 2 AN XY: 73362

African (AFR) AF: 0.0000485 AC: 2 AN: 41244

American (AMR) AF: 0.00 AC: 0 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4702

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0030
DANN	Benign	0.47
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs780907194; hg19: chr16-8988389;