rs2020920

Positions:

• chr8-42207476-T-C

Variant summary

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

The NM_000930.5(PLAT):​c.-27+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,290 control chromosomes in the GnomAD database, including 3,175 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 0.14 (3172 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3 hom.)
• Consequence: PLAT NM_000930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

PLAT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAT	NM_000930.5	c.-27+18A>G		intron_variant		ENST00000220809.9	NP_000921.1
PLAT	NM_033011.4	c.-27+18A>G		intron_variant			NP_127509.1
PLAT	NM_001319189.2	c.-27+18A>G		intron_variant			NP_001306118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.-27+18A>G		intron_variant		1	NM_000930.5	ENSP00000220809.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20794 AN: 152076 Hom.: 3152 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0938 AC: 9 AN: 96 Hom.: 3 Cov.: 0 AF XY: 0.0857 AC XY: 6 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.137 AC: 20861 AN: 152194 Hom.: 3172 Cov.: 32 AF XY: 0.131 AC XY: 9744 AN XY: 74430

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.101

Alfa AF: 0.109 Hom.: 513

Bravo AF: 0.151

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.46

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: rs2020920; hg19: chr8-42064994;