Genetic Variant USP15:c.1474-744G>A (chr12-62388687-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001252078.2(USP15):c.1474-744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,074 control chromosomes in the GnomAD database, including 4,160 homozygotes. 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 0.22 ( 4160 hom., cov: 32)

Consequence

USP15
NM_001252078.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

4 publications found

Variant links:

Genes affected

USP15 (HGNC:12613): (ubiquitin specific peptidase 15) This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]

USP15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252078.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP15	NM_001252078.2	MANE Select	c.1474-744G>A	intron	N/A	NP_001239007.1	Q9Y4E8-1
USP15	NM_006313.3		c.1387-744G>A	intron	N/A	NP_006304.1	Q9Y4E8-2
USP15	NM_001351159.2		c.1111-744G>A	intron	N/A	NP_001338088.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP15	ENST00000280377.10	TSL:1 MANE Select	c.1474-744G>A	intron	N/A	ENSP00000280377.5	Q9Y4E8-1
USP15	ENST00000353364.7	TSL:1	c.1387-744G>A	intron	N/A	ENSP00000258123.4	Q9Y4E8-2
USP15	ENST00000957648.1		c.1597-744G>A	intron	N/A	ENSP00000627707.1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34059

AN:

151956

Hom.:

4163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.224

AC:

34074

AN:

152074

Hom.:

4160

Cov.:

AF XY:

0.220

AC XY:

16360

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.335

AC:

13901

AN:

41448

American (AMR)

AF:

0.150

AC:

2292

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

448

AN:

3472

East Asian (EAS)

AF:

0.126

AC:

650

AN:

5178

South Asian (SAS)

AF:

0.210

AC:

1015

AN:

4828

European-Finnish (FIN)

AF:

0.179

AC:

1896

AN:

10568

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13191

AN:

67984

Other (OTH)

AF:

0.207

AC:

436

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1360

2721

4081

5442

6802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.179

Hom.:

1469

Bravo

AF:

0.225

Asia WGS

AF:

0.158

AC:

551

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.2

(source)

DANN

Benign

0.45

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(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