rs2020919

Positions:

• chr8-42207691-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000679300.1(PLAT):​c.-224T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,440 control chromosomes in the GnomAD database, including 5,696 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 0.18 (5694 hom., cov: 31)
  • Exomes 𝑓: 0.083 (2 hom.)
• Consequence: PLAT ENST00000679300.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

Genes affected

PLAT (HGNC:9051): (plasminogen activator, tissue type) This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAT	ENST00000679300.1	c.-224T>C		5_prime_UTR_variant	1/15
PLAT	ENST00000677722.1	n.19T>C		non_coding_transcript_exon_variant	1/13
PLAT	ENST00000352041.7			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27554 AN: 151238 Hom.: 5664 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0422

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0833 AC: 7 AN: 84 Hom.: 2 Cov.: 0 AF XY: 0.130 AC XY: 7 AN XY: 54

Gnomad4 AFR exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.183 AC: 27636 AN: 151356 Hom.: 5694 Cov.: 31 AF XY: 0.176 AC XY: 13025 AN XY: 73952

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.0422

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0772 Hom.: 1133

Bravo AF: 0.200

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2020919; hg19: chr8-42065209;