rs2227631

Variant names:

• chr7-101126257-A-G
• rs2227631
• ENST00000950058.1:c.-139A>G

Variant summary

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

The ENST00000950058.1(SERPINE1):​c.-139A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,944 control chromosomes in the GnomAD database, including 23,184 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 0.53 (23184 hom., cov: 31)
• Consequence: SERPINE1 ENST00000950058.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830
• Publications: 135 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, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000950058.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000950058.1		c.-139A>G		5_prime_UTR	Exon 3 of 12	ENSP00000620117.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80938 AN: 151826 Hom.: 23123 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.533 AC: 81060 AN: 151944 Hom.: 23184 Cov.: 31 AF XY: 0.538 AC XY: 39943 AN XY: 74234

African (AFR) AF: 0.732 AC: 30334 AN: 41446

American (AMR) AF: 0.617 AC: 9411 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3089 AN: 5162

South Asian (SAS) AF: 0.495 AC: 2378 AN: 4804

European-Finnish (FIN) AF: 0.451 AC: 4753 AN: 10546

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27918 AN: 67956

Other (OTH) AF: 0.558 AC: 1177 AN: 2110

Alfa AF: 0.457 Hom.: 60020

Bravo AF: 0.555

Asia WGS AF: 0.607 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.47
PhyloP100		0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2227631; hg19: chr7-100769538;