rs732612

chr8-42191850-G-T

Variant summary

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

The NM_000930.5(PLAT):c.73-436C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,668 control chromosomes in the GnomAD database, including 20,777 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 0.52 (20777 hom., cov: 30)
• Consequence: PLAT NM_000930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) 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.73-436C>A		intron_variant		ENST00000220809.9
PLAT	NM_001319189.2	c.73-436C>A		intron_variant
PLAT	NM_033011.4	c.73-436C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAT	ENST00000220809.9	c.73-436C>A		intron_variant		1	NM_000930.5	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78577 AN: 151550 Hom.: 20782 Cov.: 30

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.518 AC: 78603 AN: 151668 Hom.: 20777 Cov.: 30 AF XY: 0.519 AC XY: 38463 AN XY: 74094

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.542

Alfa AF: 0.537 Hom.: 3100

Bravo AF: 0.513

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.22
Dann	Benign	0.66

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: rs732612; hg19: chr8-42049368;