dbSNP rs732612: PLAT:c.73-436C>A (chr8-42191850-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

Publications

2 publications found

Variant links:

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

PLAT links:

ENSG00000304994 (HGNC:):

ENSG00000304994 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
PLAT	NM_000930.5 link	c.73-436C>A	intron_variant	Intron 2 of 13	ENST00000220809.9	NP_000921.1	P00750-1
PLAT	NM_033011.4 link	c.73-436C>A	intron_variant	Intron 2 of 12		NP_127509.1	P00750-3
PLAT	NM_001319189.2 link	c.73-436C>A	intron_variant	Intron 2 of 11		NP_001306118.1	P00750B4DN26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9 link	c.73-436C>A		intron_variant	Intron 2 of 13	1	NM_000930.5	ENSP00000220809.4		P00750-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78577

AN:

151550

Hom.:

20782

Cov.:

show subpopulations

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.:

AF XY:

0.519

AC XY:

38463

AN XY:

74094

show subpopulations

African (AFR)

AF:

0.409

AC:

16887

AN:

41294

American (AMR)

AF:

0.545

AC:

8313

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1710

AN:

3468

East Asian (EAS)

AF:

0.523

AC:

2679

AN:

5126

South Asian (SAS)

AF:

0.568

AC:

2732

AN:

4806

European-Finnish (FIN)

AF:

0.573

AC:

6001

AN:

10478

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.566

AC:

38487

AN:

67944

Other (OTH)

AF:

0.542

AC:

1144

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1861

3722

5584

7445

9306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.66

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over