8-42197628-C-T

Variant names:

• chr8-42197628-C-T
• rs879293
• NM_000930.5:c.-26-4417G>A

Variant summary

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

The NM_000930.5(PLAT):​c.-26-4417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,942 control chromosomes in the GnomAD database, including 9,524 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 0.32 (9524 hom., cov: 31)
• Consequence: PLAT NM_000930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAT	NM_000930.5	c.-26-4417G>A		intron_variant	Intron 1 of 13	ENST00000220809.9	NP_000921.1
PLAT	NM_033011.4	c.-26-4417G>A		intron_variant	Intron 1 of 12		NP_127509.1
PLAT	NM_001319189.2	c.-26-4417G>A		intron_variant	Intron 1 of 11		NP_001306118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.-26-4417G>A		intron_variant	Intron 1 of 13	1	NM_000930.5	ENSP00000220809.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48497 AN: 151824 Hom.: 9514 Cov.: 31

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.319 AC: 48517 AN: 151942 Hom.: 9524 Cov.: 31 AF XY: 0.322 AC XY: 23935 AN XY: 74248

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.337

Alfa AF: 0.368 Hom.: 4025

Bravo AF: 0.326

Asia WGS AF: 0.382 AC: 1327 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	1.2
DANN	Benign	0.57

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: rs879293; hg19: chr8-42055146;