rs2070682

Variant names:

• chr7-101133986-T-C
• rs2070682
• NM_000602.5:c.899+93T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.50
• Publications: 18 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.899+93T>C		intron_variant	Intron 5 of 8	ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.899+93T>C		intron_variant	Intron 5 of 8	1	NM_000602.5	ENSP00000223095.4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65901 AN: 151736 Hom.: 14622 Cov.: 31

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

African (AFR) AF: 0.478 AC: 12671 AN: 26498

American (AMR) AF: 0.274 AC: 11044 AN: 40240

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 10911 AN: 23748

East Asian (EAS) AF: 0.529 AC: 19580 AN: 37042

South Asian (SAS) AF: 0.405 AC: 31291 AN: 77228

European-Finnish (FIN) AF: 0.428 AC: 20799 AN: 48642

Middle Eastern (MID) AF: 0.381 AC: 1533 AN: 4028

European-Non Finnish (NFE) AF: 0.433 AC: 350386 AN: 808374

Other (OTH) AF: 0.429 AC: 20969 AN: 48922

GnomAD4 genome AF: 0.434 AC: 65928 AN: 151854 Hom.: 14628 Cov.: 31 AF XY: 0.430 AC XY: 31893 AN XY: 74202

African (AFR) AF: 0.483 AC: 20008 AN: 41400

American (AMR) AF: 0.315 AC: 4806 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1586 AN: 3464

East Asian (EAS) AF: 0.475 AC: 2448 AN: 5154

South Asian (SAS) AF: 0.417 AC: 2006 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4385 AN: 10532

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29244 AN: 67926

Other (OTH) AF: 0.392 AC: 824 AN: 2104

Alfa AF: 0.428 Hom.: 7422

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

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	-0.84
CADD	Benign	0.13
DANN	Benign	0.44
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070682; hg19: chr7-100777267; COSMIC: COSV56169253;