rs2227583

Variant names:

• chr10-73915461-T-C
• rs2227583
• NM_002658.6:c.1119+62T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-73915461-T-C
• chr10-73915461-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002658.6(PLAU):​c.1119+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,488,076 control chromosomes in the GnomAD database, including 114 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 0.0078 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (98 hom.)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00778 (1185/152260) while in subpopulation SAS AF = 0.0237 (114/4810). AF 95% confidence interval is 0.0202. There are 16 homozygotes in GnomAd4. There are 556 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAU	NM_002658.6	c.1119+62T>C		intron_variant	Intron 10 of 10	ENST00000372764.4	NP_002649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAU	ENST00000372764.4	c.1119+62T>C		intron_variant	Intron 10 of 10	1	NM_002658.6	ENSP00000361850.3

Frequencies

GnomAD3 genomes AF: 0.00782 AC: 1189 AN: 152142 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0239

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00835 AC: 11152 AN: 1335816 Hom.: 98 AF XY: 0.00916 AC XY: 6033 AN XY: 658266

African (AFR) AF: 0.00150 AC: 45 AN: 29926

American (AMR) AF: 0.00684 AC: 218 AN: 31892

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 378 AN: 20622

East Asian (EAS) AF: 0.00 AC: 0 AN: 38322

South Asian (SAS) AF: 0.0279 AC: 1984 AN: 71122

European-Finnish (FIN) AF: 0.00681 AC: 339 AN: 49794

Middle Eastern (MID) AF: 0.0422 AC: 156 AN: 3700

European-Non Finnish (NFE) AF: 0.00719 AC: 7442 AN: 1035316

Other (OTH) AF: 0.0107 AC: 590 AN: 55122

GnomAD4 genome AF: 0.00778 AC: 1185 AN: 152260 Hom.: 16 Cov.: 32 AF XY: 0.00747 AC XY: 556 AN XY: 74446

African (AFR) AF: 0.00168 AC: 70 AN: 41546

American (AMR) AF: 0.00778 AC: 119 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 63 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0237 AC: 114 AN: 4810

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 725 AN: 68022

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00588 Hom.: 4

Bravo AF: 0.00694

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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: rs2227583; hg19: chr10-75675219;