rs10158897

Positions:

• chr1-62447248-C-T

Variant summary

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

The NM_003368.5(USP1):​c.1250-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,205,848 control chromosomes in the GnomAD database, including 69,892 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 0.33 (8283 hom., cov: 33)
  • Exomes 𝑓: 0.34 (61609 hom.)
• Consequence: USP1 NM_003368.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

Genes affected

USP1 (HGNC:12607): (ubiquitin specific peptidase 1) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. The protein specifically deubiquitinates a protein in the Fanconi anemia (FA) DNA repair pathway. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP1	NM_003368.5	c.1250-93C>T		intron_variant		ENST00000339950.5	NP_003359.3
USP1	NM_001017415.2	c.1250-93C>T		intron_variant			NP_001017415.1
USP1	NM_001017416.2	c.1250-93C>T		intron_variant			NP_001017416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP1	ENST00000339950.5	c.1250-93C>T		intron_variant		1	NM_003368.5	ENSP00000343526.4
USP1	ENST00000371146.5	c.1250-93C>T		intron_variant		5		ENSP00000360188.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49723 AN: 151948 Hom.: 8274 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.336 AC: 354261 AN: 1053782 Hom.: 61609 AF XY: 0.339 AC XY: 177747 AN XY: 525030

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.327 AC: 49757 AN: 152066 Hom.: 8283 Cov.: 33 AF XY: 0.326 AC XY: 24238 AN XY: 74344

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.295

Alfa AF: 0.322 Hom.: 7946

Bravo AF: 0.332

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10158897; hg19: chr1-62912919;