rs2167287

Positions:

• chr12-62388687-G-A
• chr12-62388687-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP15	NM_001252078.2	c.1474-744G>A		intron_variant		ENST00000280377.10	NP_001239007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP15	ENST00000280377.10	c.1474-744G>A		intron_variant		1	NM_001252078.2	ENSP00000280377.5
USP15	ENST00000353364.7	c.1387-744G>A		intron_variant		1		ENSP00000258123.4
USP15	ENST00000549268.1	n.832-744G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34059 AN: 151956 Hom.: 4163 Cov.: 32

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.: 32 AF XY: 0.220 AC XY: 16360 AN XY: 74336

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.207

Alfa AF: 0.176 Hom.: 1283

Bravo AF: 0.225

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs2167287; hg19: chr12-62782467;