Variant rs7242 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.*722T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 155,402 control chromosomes in the GnomAD database, including 15,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14846 hom., cov: 32)

Exomes 𝑓: 0.37 ( 256 hom. )

Consequence

SERPINE1
NM_000602.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.205

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 7-101138164-T-G is Benign according to our data. Variant chr7-101138164-T-G is described in ClinVar as [Benign]. Clinvar id is 358319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 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.*722T>G		3_prime_UTR_variant	9/9	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.*722T>G		3_prime_UTR_variant	9/9	1	NM_000602.5	ENSP00000223095.4		P05121-1

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66416

AN:

151876

Hom.:

14838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.365

AC:

1244

AN:

3408

Hom.:

256

Cov.:

AF XY:

0.369

AC XY:

650

AN XY:

1760

show subpopulations

Gnomad4 AFR exome

AF:

0.368

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.437

AC:

66445

AN:

151994

Hom.:

14846

Cov.:

AF XY:

0.433

AC XY:

32133

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.416

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.398

Alfa

AF:

0.429

Hom.:

29360

Bravo

AF:

0.435

Asia WGS

AF:

0.378

AC:

1315

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.84

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