rs2823482

Variant names:

• chr21-15772692-G-A
• rs2823482
• NM_001283041.3:c.269-5212G>A

Variant summary

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

The NM_001283041.3(USP25):​c.269-5212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,066 control chromosomes in the GnomAD database, including 7,440 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 0.29 (7440 hom., cov: 33)
• Consequence: USP25 NM_001283041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 0 publications found

Genes affected

USP25 (HGNC:12624): (ubiquitin specific peptidase 25) Ubiquitin (MIM 191339) is a highly conserved 76-amino acid protein involved in regulation of intracellular protein breakdown, cell cycle regulation, and stress response. Ubiquitin is released from degraded proteins by disassembly of the polyubiquitin chains, which is mediated by ubiquitin-specific proteases (USPs), such as USP25 (Valero et al., 1999 [PubMed 10644437]).[supplied by OMIM, Mar 2008]

USP25 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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 = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283041.3. 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
	USP25	NM_001283041.3	MANE Select	c.269-5212G>A		intron	N/A	NP_001269970.1	Q9UHP3-3
	USP25	NM_001283042.3		c.269-5212G>A		intron	N/A	NP_001269971.1	Q9UHP3-1
	USP25	NM_013396.6		c.269-5212G>A		intron	N/A	NP_037528.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP25	ENST00000400183.7	TSL:1 MANE Select	c.269-5212G>A		intron	N/A	ENSP00000383044.2	Q9UHP3-3
	USP25	ENST00000285681.6	TSL:1	c.269-5212G>A		intron	N/A	ENSP00000285681.2	Q9UHP3-1
	USP25	ENST00000285679.10	TSL:1	c.269-5212G>A		intron	N/A	ENSP00000285679.6	Q9UHP3-2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44361 AN: 151948 Hom.: 7414 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.292 AC: 44433 AN: 152066 Hom.: 7440 Cov.: 33 AF XY: 0.290 AC XY: 21531 AN XY: 74330

African (AFR) AF: 0.470 AC: 19479 AN: 41478

American (AMR) AF: 0.214 AC: 3277 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2457 AN: 10552

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15149 AN: 67970

Other (OTH) AF: 0.269 AC: 568 AN: 2114

Alfa AF: 0.234 Hom.: 3599

Bravo AF: 0.298

Asia WGS AF: 0.225 AC: 783 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		0.14
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: rs2823482; hg19: chr21-17145011;