chr7-101128442-G-A

Position:

chr7-101128442-G-A

Variant summary

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

The NM_000602.5(SERPINE1):c.49G>A(p.Val17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,614,080 control chromosomes in the GnomAD database, including 512 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 118 hom., cov: 32)

Exomes 𝑓: 0.015 ( 394 hom. )

Consequence

SERPINE1
NM_000602.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.62

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 (MetaRNN=0.0027550757).

BP6

Variant 7-101128442-G-A is Benign according to our data. Variant chr7-101128442-G-A is described in ClinVar as [Benign]. Clinvar id is 358307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-101128442-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 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.49G>A	p.Val17Ile	missense_variant	2/9	ENST00000223095.5	NP_000593.1	P05121-1A0A024QYT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5 linkuse as main transcript	c.49G>A	p.Val17Ile	missense_variant	2/9	1	NM_000602.5	ENSP00000223095.4		P05121-1

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4978

AN:

152130

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0486

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0374

GnomAD3 exomes

AF:

0.0287

AC:

7211

AN:

251170

Hom.:

192

AF XY:

0.0261

AC XY:

3550

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.0647

Gnomad AMR exome

AF:

0.0530

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.0512

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.0598

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0266

GnomAD4 exome

AF:

0.0154

AC:

22541

AN:

1461832

Hom.:

394

Cov.:

AF XY:

0.0151

AC XY:

10982

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0650

Gnomad4 AMR exome

AF:

0.0499

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.0563

Gnomad4 NFE exome

AF:

0.00949

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0327

AC:

4981

AN:

152248

Hom.:

118

Cov.:

AF XY:

0.0345

AC XY:

2565

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.0485

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0338

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.0672

AC:

296

ESP6500EA

AF:

0.00953

AC:

ExAC

AF:

0.0271

AC:

3289

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

EpiCase

AF:

0.0114

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 09, 2021	- -

Congenital plasminogen activator inhibitor type 1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.0090

DANN

Benign

0.35

DEOGEN2

Benign

0.15

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.26

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.010

REVEL

Benign

0.14

Sift

Benign

0.64

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.0060

MPC

0.18

ClinPred

0.00030

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.095

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