7-101133650-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000602.5(SERPINE1):c.701-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,589,982 control chromosomes in the GnomAD database, including 147,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14595 hom., cov: 32)

Exomes 𝑓: 0.43 ( 132771 hom. )

Consequence

SERPINE1
NM_000602.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.691

Publications

25 publications found

Variant links:

Genes affected

SERPINE1 (HGNC:8583): (serpin family E member 1) This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The protein also functions as a component of innate antiviral immunity. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. [provided by RefSeq, Aug 2020]

SERPINE1 Gene-Disease associations (from GenCC):

congenital plasminogen activator inhibitor type 1 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

SERPINE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-101133650-G-A is Benign according to our data. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101133650-G-A is described in CliVar as Benign. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5 link	c.701-45G>A		intron_variant	Intron 4 of 8	ENST00000223095.5	NP_000593.1	P05121-1A0A024QYT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5 link	c.701-45G>A		intron_variant	Intron 4 of 8	1	NM_000602.5	ENSP00000223095.4		P05121-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65839

AN:

151916

Hom.:

14589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.393

GnomAD2 exomes

AF:

0.408

AC:

101733

AN:

249100

AF XY:

0.412

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.427

AC:

613931

AN:

1437948

Hom.:

132771

Cov.:

AF XY:

0.427

AC XY:

305716

AN XY:

716650

show subpopulations

African (AFR)

AF:

0.474

AC:

15606

AN:

32952

American (AMR)

AF:

0.265

AC:

11853

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11942

AN:

26010

East Asian (EAS)

AF:

0.524

AC:

20729

AN:

39568

South Asian (SAS)

AF:

0.405

AC:

34711

AN:

85758

European-Finnish (FIN)

AF:

0.428

AC:

22773

AN:

53264

Middle Eastern (MID)

AF:

0.372

AC:

2123

AN:

5712

European-Non Finnish (NFE)

AF:

0.430

AC:

468805

AN:

1090452

Other (OTH)

AF:

0.426

AC:

25389

AN:

59580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

18091

36182

54272

72363

90454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14156

28312

42468

56624

70780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.433

AC:

65865

AN:

152034

Hom.:

14595

Cov.:

AF XY:

0.429

AC XY:

31867

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.482

AC:

19960

AN:

41450

American (AMR)

AF:

0.311

AC:

4753

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1586

AN:

3468

East Asian (EAS)

AF:

0.474

AC:

2452

AN:

5170

South Asian (SAS)

AF:

0.417

AC:

2012

AN:

4822

European-Finnish (FIN)

AF:

0.416

AC:

4404

AN:

10576

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.430

AC:

29254

AN:

67966

Other (OTH)

AF:

0.390

AC:

823

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1859

3719

5578

7438

9297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.429

Hom.:

45711

Bravo

AF:

0.430

Asia WGS

AF:

0.378

AC:

1316

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.064

(source)

DANN

Benign

0.77

PhyloP100

-0.69

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over