rs2227667

Variant names:

• chr7-101131468-A-G
• rs2227667
• NM_000602.5:c.506-407A>G

Variant summary

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

The NM_000602.5(SERPINE1):​c.506-407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,784 control chromosomes in the GnomAD database, including 5,324 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 0.25 (5324 hom., cov: 31)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 33 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000602.5. 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
	SERPINE1	NM_000602.5	MANE Select	c.506-407A>G		intron	N/A	NP_000593.1	P05121-1
	SERPINE1	NM_001386460.1		c.506-407A>G		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.506-407A>G		intron	N/A	NP_001373390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000223095.5	TSL:1 MANE Select	c.506-407A>G		intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.530-407A>G		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.506-407A>G		intron	N/A	ENSP00000620121.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38216 AN: 151666 Hom.: 5305 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.252 AC: 38263 AN: 151784 Hom.: 5324 Cov.: 31 AF XY: 0.259 AC XY: 19243 AN XY: 74160

African (AFR) AF: 0.240 AC: 9932 AN: 41366

American (AMR) AF: 0.412 AC: 6271 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 948 AN: 3464

East Asian (EAS) AF: 0.440 AC: 2253 AN: 5120

South Asian (SAS) AF: 0.358 AC: 1722 AN: 4816

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14388 AN: 67936

Other (OTH) AF: 0.299 AC: 630 AN: 2110

Alfa AF: 0.243 Hom.: 2008

Bravo AF: 0.267

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-0.82
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: rs2227667; hg19: chr7-100774749;