rs1058720

Positions:

• chr8-42187436-G-A
• chr8-42187436-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000930.5(PLAT):​c.501C>T​(p.Asp167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,599,912 control chromosomes in the GnomAD database, including 252,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.52 (20670 hom., cov: 34)
  • Exomes 𝑓: 0.57 (232175 hom.)
• Consequence: PLAT NM_000930.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-42187436-G-A is Benign according to our data. Variant chr8-42187436-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.266 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAT	NM_000930.5	c.501C>T	p.Asp167=	synonymous_variant	6/14	ENST00000220809.9
PLAT	NM_033011.4	c.363C>T	p.Asp121=	synonymous_variant	5/13
PLAT	NM_001319189.2	c.364+470C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAT	ENST00000220809.9	c.501C>T	p.Asp167=	synonymous_variant	6/14	1	NM_000930.5	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78404 AN: 152110 Hom.: 20674 Cov.: 34

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.544

GnomAD3 exomes AF: 0.550 AC: 133028 AN: 241960 Hom.: 37016 AF XY: 0.553 AC XY: 72634 AN XY: 131446

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.497

Gnomad EAS exome AF: 0.522

Gnomad SAS exome AF: 0.562

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.565 AC: 818148 AN: 1447684 Hom.: 232175 Cov.: 48 AF XY: 0.564 AC XY: 406534 AN XY: 720290

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.515 AC: 78430 AN: 152228 Hom.: 20670 Cov.: 34 AF XY: 0.516 AC XY: 38410 AN XY: 74420

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.539

Alfa AF: 0.552 Hom.: 41156

Bravo AF: 0.509

Asia WGS AF: 0.522 AC: 1816 AN: 3478

EpiCase AF: 0.564

EpiControl AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.073
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058720; hg19: chr8-42044954; COSMIC: COSV54274776; COSMIC: COSV54274776;