8-42198531-C-G

Position:

• chr8-42198531-C-G

Variant summary

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

The ENST00000220809.9(PLAT):​c.-26-5320G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,128 control chromosomes in the GnomAD database, including 23,936 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 0.55 (23936 hom., cov: 33)
• Consequence: PLAT ENST00000220809.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAT	NM_000930.5	c.-26-5320G>C		intron_variant		ENST00000220809.9	NP_000921.1
PLAT	NM_001319189.2	c.-26-5320G>C		intron_variant			NP_001306118.1
PLAT	NM_033011.4	c.-26-5320G>C		intron_variant			NP_127509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.-26-5320G>C		intron_variant		1	NM_000930.5	ENSP00000220809	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82978 AN: 152010 Hom.: 23922 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 83013 AN: 152128 Hom.: 23936 Cov.: 33 AF XY: 0.553 AC XY: 41126 AN XY: 74370

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.568

Alfa AF: 0.476 Hom.: 1560

Bravo AF: 0.535

Asia WGS AF: 0.617 AC: 2146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.68

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: rs2299609; hg19: chr8-42056049; COSMIC: COSV54278422; COSMIC: COSV54278422;