rs2020922

Variant names:

• chr8-42180406-T-A
• rs2020922
• NM_000930.5:c.1086-28A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-42180406-T-A
• chr8-42180406-T-C
• chr8-42180406-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000930.5(PLAT):​c.1086-28A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,613,618 control chromosomes in the GnomAD database, including 432,381 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 0.78 (47248 hom., cov: 34)
  • Exomes 𝑓: 0.72 (385133 hom.)
• Consequence: PLAT NM_000930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 15 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: AR, AD Classification: MODERATE, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

ENSG00000304994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAT	NM_000930.5	c.1086-28A>T		intron_variant	Intron 10 of 13	ENST00000220809.9	NP_000921.1
PLAT	NM_033011.4	c.948-28A>T		intron_variant	Intron 9 of 12		NP_127509.1
PLAT	NM_001319189.2	c.819-28A>T		intron_variant	Intron 8 of 11		NP_001306118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.1086-28A>T		intron_variant	Intron 10 of 13	1	NM_000930.5	ENSP00000220809.4

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118709 AN: 152140 Hom.: 47202 Cov.: 34

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.759

GnomAD2 exomes AF: 0.735 AC: 184569 AN: 251108 AF XY: 0.736

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.638

Gnomad EAS exome AF: 0.748

Gnomad FIN exome AF: 0.764

Gnomad NFE exome AF: 0.710

Gnomad OTH exome AF: 0.714

GnomAD4 exome AF: 0.725 AC: 1058806 AN: 1461360 Hom.: 385133 Cov.: 48 AF XY: 0.725 AC XY: 527269 AN XY: 726974

African (AFR) AF: 0.954 AC: 31943 AN: 33474

American (AMR) AF: 0.671 AC: 30006 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 16656 AN: 26134

East Asian (EAS) AF: 0.739 AC: 29355 AN: 39700

South Asian (SAS) AF: 0.793 AC: 68355 AN: 86248

European-Finnish (FIN) AF: 0.762 AC: 40689 AN: 53380

Middle Eastern (MID) AF: 0.694 AC: 4002 AN: 5766

European-Non Finnish (NFE) AF: 0.714 AC: 793141 AN: 1111566

Other (OTH) AF: 0.740 AC: 44659 AN: 60370

GnomAD4 genome AF: 0.780 AC: 118810 AN: 152258 Hom.: 47248 Cov.: 34 AF XY: 0.780 AC XY: 58073 AN XY: 74424

African (AFR) AF: 0.949 AC: 39446 AN: 41574

American (AMR) AF: 0.697 AC: 10669 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3868 AN: 5170

South Asian (SAS) AF: 0.805 AC: 3882 AN: 4820

European-Finnish (FIN) AF: 0.760 AC: 8052 AN: 10598

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.709 AC: 48240 AN: 68008

Other (OTH) AF: 0.756 AC: 1598 AN: 2114

Alfa AF: 0.676 Hom.: 4110

Bravo AF: 0.779

Asia WGS AF: 0.796 AC: 2771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.91
DANN	Benign	0.41
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2020922; hg19: chr8-42037924;