chr21-15772692-G-A

Position:

• chr21-15772692-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP25	NM_001283041.3	c.269-5212G>A		intron_variant		ENST00000400183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP25	ENST00000400183.7	c.269-5212G>A		intron_variant		1	NM_001283041.3	A1
USP25	ENST00000285679.10	c.269-5212G>A		intron_variant		1		P3
USP25	ENST00000285681.6	c.269-5212G>A		intron_variant		1
USP25	ENST00000351097.9	c.269-5212G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.269

Alfa AF: 0.233 Hom.: 2474

Bravo AF: 0.298

Asia WGS AF: 0.225 AC: 783 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.71

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: rs2823482; hg19: chr21-17145011;