rs2020922

Positions:

• chr8-42180406-T-A
• chr8-42180406-T-C
• chr8-42180406-T-G

Variant summary

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

The NM_000930.5(PLAT):​c.1086-28A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,613,618 control chromosomes in the GnomAD database, including 432,381 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 0.78 (47248 hom., cov: 34)
  • Exomes 𝑓: 0.72 (385133 hom.)
• Consequence: PLAT NM_000930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAT	NM_000930.5	c.1086-28A>T		intron_variant		ENST00000220809.9
PLAT	NM_001319189.2	c.819-28A>T		intron_variant
PLAT	NM_033011.4	c.948-28A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAT	ENST00000220809.9	c.1086-28A>T		intron_variant		1	NM_000930.5	P1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118709 AN: 152140 Hom.: 47202 Cov.: 34

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.759

GnomAD3 exomes AF: 0.735 AC: 184569 AN: 251108 Hom.: 68578 AF XY: 0.736 AC XY: 99822 AN XY: 135710

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.638

Gnomad EAS exome AF: 0.748

Gnomad SAS exome AF: 0.798

Gnomad FIN exome AF: 0.764

Gnomad NFE exome AF: 0.710

Gnomad OTH exome AF: 0.714

GnomAD4 exome AF: 0.725 AC: 1058806 AN: 1461360 Hom.: 385133 Cov.: 48 AF XY: 0.725 AC XY: 527269 AN XY: 726974

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.714

Gnomad4 OTH exome AF: 0.740

GnomAD4 genome AF: 0.780 AC: 118810 AN: 152258 Hom.: 47248 Cov.: 34 AF XY: 0.780 AC XY: 58073 AN XY: 74424

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.756

Alfa AF: 0.676 Hom.: 4110

Bravo AF: 0.779

Asia WGS AF: 0.796 AC: 2771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.91
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2020922; hg19: chr8-42037924;