rs2227553

Variant names:

• chr10-73910185-A-C
• rs2227553
• ENST00000409178.5:n.2297T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-73910185-A-C
• chr10-73910185-A-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+891A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,264 control chromosomes in the GnomAD database, including 814 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 0.065 (814 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLAU NM_001441154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 5 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• Quebec platelet disorder

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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+891A>C		intron	N/A	NP_001428083.1
	C10orf55	NR_160937.1		n.2426T>G		non_coding_transcript_exon	Exon 6 of 6
	C10orf55	NR_160938.1		n.2297T>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C10orf55	ENST00000409178.5	TSL:1	n.2297T>G		non_coding_transcript_exon	Exon 5 of 5
	PLAU	ENST00000481390.5	TSL:2	c.-32+891A>C		intron	N/A	ENSP00000474318.1	S4R3G7
	C10orf55	ENST00000721915.1		n.269-1732T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9939 AN: 152146 Hom.: 808 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00994

Gnomad OTH AF: 0.0455

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0654 AC: 9960 AN: 152264 Hom.: 814 Cov.: 33 AF XY: 0.0634 AC XY: 4720 AN XY: 74452

African (AFR) AF: 0.194 AC: 8067 AN: 41516

American (AMR) AF: 0.0312 AC: 477 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3472

East Asian (EAS) AF: 0.0557 AC: 289 AN: 5184

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4828

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00994 AC: 676 AN: 68020

Other (OTH) AF: 0.0445 AC: 94 AN: 2110

Alfa AF: 0.0432 Hom.: 683

Bravo AF: 0.0735

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		3.2
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: rs2227553; hg19: chr10-75669943;