rs2227666

Variant names:

• chr7-101131424-G-A
• rs2227666
• NM_000602.5:c.506-451G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000602.5(SERPINE1):​c.506-451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 151,724 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.037 (147 hom., cov: 32)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.506-451G>A		intron_variant	Intron 3 of 8	ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.506-451G>A		intron_variant	Intron 3 of 8	1	NM_000602.5	ENSP00000223095.4

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5645 AN: 151602 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0372 AC: 5646 AN: 151724 Hom.: 147 Cov.: 32 AF XY: 0.0362 AC XY: 2683 AN XY: 74130

African (AFR) AF: 0.0135 AC: 560 AN: 41380

American (AMR) AF: 0.0371 AC: 564 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3470

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5086

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4794

European-Finnish (FIN) AF: 0.0462 AC: 487 AN: 10542

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0562 AC: 3817 AN: 67930

Other (OTH) AF: 0.0394 AC: 83 AN: 2104

Alfa AF: 0.0454 Hom.: 27

Bravo AF: 0.0362

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs2227666; hg19: chr7-100774705;