10-73909561-C-T

Variant names:

• chr10-73909561-C-T
• rs2227552
• NM_001441154.1:c.-32+267C>T

Variant summary

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

The NM_001441154.1(PLAU):​c.-32+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,092 control chromosomes in the GnomAD database, including 40,711 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 0.73 (40711 hom., cov: 32)
• Consequence: PLAU NM_001441154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 7 publications found

Genes affected

PLAU (HGNC:9052): (plasminogen activator, urokinase) This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

C10orf55 (HGNC:31008): (chromosome 10 putative open reading frame 55) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441154.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	NM_001441154.1		c.-32+267C>T		intron	N/A	NP_001428083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	ENST00000481390.5	TSL:2	c.-32+267C>T		intron	N/A	ENSP00000474318.1
	C10orf55	ENST00000721923.1		n.86G>A		non_coding_transcript_exon	Exon 1 of 2
	C10orf55	ENST00000721915.1		n.269-1108G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110242 AN: 151974 Hom.: 40676 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.725 AC: 110318 AN: 152092 Hom.: 40711 Cov.: 32 AF XY: 0.715 AC XY: 53161 AN XY: 74316

African (AFR) AF: 0.805 AC: 33436 AN: 41512

American (AMR) AF: 0.600 AC: 9157 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3115 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2475 AN: 5156

South Asian (SAS) AF: 0.592 AC: 2858 AN: 4824

European-Finnish (FIN) AF: 0.627 AC: 6613 AN: 10550

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50186 AN: 67986

Other (OTH) AF: 0.757 AC: 1601 AN: 2114

Alfa AF: 0.737 Hom.: 157673

Bravo AF: 0.729

Asia WGS AF: 0.526 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.39
PhyloP100		-0.60
PromoterAI		-0.048	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2227552; hg19: chr10-75669319;