Genetic Variant PLAU:c.-32+267C>T (chr10-73909561-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.596

Publications

7 publications found

Variant links:

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]

PLAU links:

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

C10orf55 links:

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ACMG classification

Classification was made for transcript

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

Sel.	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLAU	ENST00000481390.5	TSL:2	c.-32+267C>T	intron	N/A	ENSP00000474318.1	S4R3G7
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.:

show subpopulations

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.:

AF XY:

0.715

AC XY:

53161

AN XY:

74316

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1487

2975

4462

5950

7437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.39

PhyloP100

-0.60

PromoterAI

-0.048

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over