rs2227684

Variant names:

• chr7-101133650-G-A
• rs2227684
• NM_000602.5:c.701-45G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101133650-G-A
• chr7-101133650-G-T

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.691
• Publications: 25 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=-0.8).
• BP6: Variant 7-101133650-G-A is Benign according to our data. Variant chr7-101133650-G-A is described in ClinVar 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	c.701-45G>A		intron_variant	Intron 4 of 8	ENST00000223095.5	NP_000593.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65839 AN: 151916 Hom.: 14589 Cov.: 32

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

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.: 28 AF XY: 0.427 AC XY: 305716 AN XY: 716650

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

GnomAD4 genome AF: 0.433 AC: 65865 AN: 152034 Hom.: 14595 Cov.: 32 AF XY: 0.429 AC XY: 31867 AN XY: 74328

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

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

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
DANN	Benign	0.77
PhyloP100		-0.69
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: rs2227684; hg19: chr7-100776931; COSMIC: COSV56169612;