chr8-42197628-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• thrombophilia, familial, due to decreased release of tissue plasminogen activator

  Inheritance: AD, AR Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp

ENSG00000304994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAT	NM_000930.5	MANE Select	c.-26-4417G>A		intron	N/A	NP_000921.1	P00750-1
	PLAT	NM_033011.4		c.-26-4417G>A		intron	N/A	NP_127509.1	P00750-3
	PLAT	NM_001319189.2		c.-26-4417G>A		intron	N/A	NP_001306118.1	B4DN26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAT	ENST00000220809.9	TSL:1 MANE Select	c.-26-4417G>A		intron	N/A	ENSP00000220809.4	P00750-1
	PLAT	ENST00000352041.7	TSL:1	c.-26-4417G>A		intron	N/A	ENSP00000270188.6	P00750-3
	PLAT	ENST00000679300.1		c.-26-4417G>A		intron	N/A	ENSP00000503050.1	A0A7I2YQ93

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

African (AFR) AF: 0.0891 AC: 3696 AN: 41488

American (AMR) AF: 0.501 AC: 7653 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2687 AN: 5150

South Asian (SAS) AF: 0.401 AC: 1927 AN: 4810

European-Finnish (FIN) AF: 0.322 AC: 3389 AN: 10532

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26860 AN: 67932

Other (OTH) AF: 0.337 AC: 708 AN: 2104

Alfa AF: 0.324 Hom.: 6627

Bravo AF: 0.326

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs879293; hg19: chr8-42055146;