chr12-62388687-G-A

Variant names:

• chr12-62388687-G-A
• rs2167287
• NM_001252078.2:c.1474-744G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACMG classification

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	ENST00000280377.10	TSL:1 MANE Select	c.1474-744G>A		intron	N/A	ENSP00000280377.5
	USP15	ENST00000353364.7	TSL:1	c.1387-744G>A		intron	N/A	ENSP00000258123.4
	USP15	ENST00000549268.1	TSL:5	n.832-744G>A		intron	N/A

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

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: 49 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13191 AN: 67984

Other (OTH) AF: 0.207 AC: 436 AN: 2104

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
DANN	Benign	0.45
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs2167287; hg19: chr12-62782467;