chr12-62275632-A-G

Variant names:

• chr12-62275632-A-G
• rs7315790
• NM_001252078.2:c.89+15129A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252078.2(USP15):​c.89+15129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 151,934 control chromosomes in the GnomAD database, including 56,168 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 0.86 (56168 hom., cov: 29)
• Consequence: USP15 NM_001252078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 3 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]

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	NM_001252078.2	MANE Select	c.89+15129A>G		intron	N/A	NP_001239007.1	Q9Y4E8-1
	USP15	NM_006313.3		c.89+15129A>G		intron	N/A	NP_006304.1	Q9Y4E8-2
	USP15	NM_001351159.2		c.-1661+15129A>G		intron	N/A	NP_001338088.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	ENST00000280377.10	TSL:1 MANE Select	c.89+15129A>G		intron	N/A	ENSP00000280377.5	Q9Y4E8-1
	USP15	ENST00000353364.7	TSL:1	c.89+15129A>G		intron	N/A	ENSP00000258123.4	Q9Y4E8-2
	USP15	ENST00000312635.10	TSL:1	c.89+15129A>G		intron	N/A	ENSP00000309240.6	Q9Y4E8-4

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130228 AN: 151816 Hom.: 56111 Cov.: 29

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.858 AC: 130342 AN: 151934 Hom.: 56168 Cov.: 29 AF XY: 0.857 AC XY: 63611 AN XY: 74258

African (AFR) AF: 0.928 AC: 38448 AN: 41432

American (AMR) AF: 0.782 AC: 11910 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3115 AN: 3466

East Asian (EAS) AF: 0.708 AC: 3645 AN: 5148

South Asian (SAS) AF: 0.784 AC: 3776 AN: 4816

European-Finnish (FIN) AF: 0.888 AC: 9391 AN: 10576

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57269 AN: 67952

Other (OTH) AF: 0.850 AC: 1788 AN: 2104

Alfa AF: 0.839 Hom.: 23303

Bravo AF: 0.853

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.36
PhyloP100		0.027
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: rs7315790; hg19: chr12-62669413;