rs10158897

Variant names:

• chr1-62447248-C-T
• rs10158897
• NM_003368.5:c.1250-93C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 publications found

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]

USP1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003368.5. 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
	USP1	NM_003368.5	MANE Select	c.1250-93C>T		intron	N/A	NP_003359.3
	USP1	NM_001017415.2		c.1250-93C>T		intron	N/A	NP_001017415.1
	USP1	NM_001017416.2		c.1250-93C>T		intron	N/A	NP_001017416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP1	ENST00000339950.5	TSL:1 MANE Select	c.1250-93C>T		intron	N/A	ENSP00000343526.4
	USP1	ENST00000956643.1		c.1250-93C>T		intron	N/A	ENSP00000626702.1
	USP1	ENST00000371146.5	TSL:5	c.1250-93C>T		intron	N/A	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

African (AFR) AF: 0.344 AC: 7955 AN: 23132

American (AMR) AF: 0.351 AC: 7335 AN: 20896

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 3963 AN: 17638

East Asian (EAS) AF: 0.166 AC: 5701 AN: 34290

South Asian (SAS) AF: 0.430 AC: 24403 AN: 56776

European-Finnish (FIN) AF: 0.259 AC: 11568 AN: 44668

Middle Eastern (MID) AF: 0.285 AC: 1079 AN: 3780

European-Non Finnish (NFE) AF: 0.344 AC: 277455 AN: 807152

Other (OTH) AF: 0.326 AC: 14802 AN: 45450

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

African (AFR) AF: 0.352 AC: 14597 AN: 41440

American (AMR) AF: 0.333 AC: 5097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3472

East Asian (EAS) AF: 0.193 AC: 1003 AN: 5188

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4826

European-Finnish (FIN) AF: 0.250 AC: 2638 AN: 10570

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22540 AN: 67976

Other (OTH) AF: 0.295 AC: 620 AN: 2100

Alfa AF: 0.323 Hom.: 10877

Bravo AF: 0.332

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10158897; hg19: chr1-62912919;