Variant rs2070682 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000602.5(SERPINE1):c.899+93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,266,576 control chromosomes in the GnomAD database, including 118,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14628 hom., cov: 31)

Exomes 𝑓: 0.43 ( 104313 hom. )

Consequence

SERPINE1
NM_000602.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.50

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-101133986-T-C is Benign according to our data. Variant chr7-101133986-T-C is described in ClinVar as [Benign]. Clinvar id is 1273479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE1	NM_000602.5 linkuse as main transcript	c.899+93T>C		intron_variant		ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5 linkuse as main transcript	c.899+93T>C		intron_variant		1	NM_000602.5	ENSP00000223095	P1	P05121-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65901

AN:

151736

Hom.:

14622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.394

GnomAD4 exome

AF:

0.430

AC:

479184

AN:

1114722

Hom.:

104313

AF XY:

0.429

AC XY:

243702

AN XY:

568044

show subpopulations

Gnomad4 AFR exome

AF:

0.478

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.529

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.429

GnomAD4 genome

AF:

0.434

AC:

65928

AN:

151854

Hom.:

14628

Cov.:

AF XY:

0.430

AC XY:

31893

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.483

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.416

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.427

Hom.:

6657

Bravo

AF:

0.432

Asia WGS

AF:

0.379

AC:

1318

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.13

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over