rs2227571

Variant names:

• chr10-73914982-C-T
• rs2227571
• NM_002658.6:c.970+66C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-73914982-C-T
• chr10-73914982-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002658.6(PLAU):​c.970+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,541,064 control chromosomes in the GnomAD database, including 203,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15551 hom., cov: 32)
  • Exomes 𝑓: 0.51 (188427 hom.)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-73914982-C-T is Benign according to our data. Variant chr10-73914982-C-T is described in ClinVar as Benign. ClinVar VariationId is 1227450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002658.6. 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_002658.6	MANE Select	c.970+66C>T		intron	N/A	NP_002649.2	P00749-1
	PLAU	NM_001441154.1		c.970+66C>T		intron	N/A	NP_001428083.1
	PLAU	NM_001441155.1		c.970+66C>T		intron	N/A	NP_001428084.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	ENST00000372764.4	TSL:1 MANE Select	c.970+66C>T		intron	N/A	ENSP00000361850.3	P00749-1
	C10orf55	ENST00000409178.5	TSL:1	n.268+1537G>A		intron	N/A
	PLAU	ENST00000894723.1		c.970+66C>T		intron	N/A	ENSP00000564782.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64994 AN: 151830 Hom.: 15554 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.507 AC: 704875 AN: 1389116 Hom.: 188427 AF XY: 0.504 AC XY: 348768 AN XY: 691798

African (AFR) AF: 0.242 AC: 7827 AN: 32342

American (AMR) AF: 0.309 AC: 13353 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 13463 AN: 24092

East Asian (EAS) AF: 0.108 AC: 4250 AN: 39378

South Asian (SAS) AF: 0.297 AC: 23807 AN: 80258

European-Finnish (FIN) AF: 0.459 AC: 22923 AN: 49964

Middle Eastern (MID) AF: 0.599 AC: 3350 AN: 5596

European-Non Finnish (NFE) AF: 0.556 AC: 587413 AN: 1056308

Other (OTH) AF: 0.491 AC: 28489 AN: 58010

GnomAD4 genome AF: 0.428 AC: 64998 AN: 151948 Hom.: 15551 Cov.: 32 AF XY: 0.422 AC XY: 31372 AN XY: 74258

African (AFR) AF: 0.246 AC: 10189 AN: 41418

American (AMR) AF: 0.429 AC: 6554 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1971 AN: 3466

East Asian (EAS) AF: 0.115 AC: 592 AN: 5160

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4826

European-Finnish (FIN) AF: 0.466 AC: 4911 AN: 10534

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37743 AN: 67952

Other (OTH) AF: 0.496 AC: 1046 AN: 2108

Alfa AF: 0.338 Hom.: 1006

Bravo AF: 0.419

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		1.0
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: rs2227571; hg19: chr10-75674740; COSMIC: COSV65641616; COSMIC: COSV65641616;