7-101136660-A-T

Variant names:

• chr7-101136660-A-T
• rs2070683
• NM_000602.5:c.1088-341A>T

Variant summary

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

The NM_001386460.1(SERPINE1):​c.1088-341A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,488 control chromosomes in the GnomAD database, including 14,300 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 0.43 (14300 hom., cov: 31)
• Consequence: SERPINE1 NM_001386460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386460.1. 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
	SERPINE1	NM_000602.5	MANE Select	c.1088-341A>T		intron	N/A	NP_000593.1
	SERPINE1	NM_001386460.1		c.1088-341A>T		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.1087+859A>T		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.1088-341A>T		intron	N/A	ENSP00000223095.4
	SERPINE1	ENST00000950060.1		c.1112-341A>T		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.1103-341A>T		intron	N/A	ENSP00000620121.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65230 AN: 151374 Hom.: 14293 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.431 AC: 65256 AN: 151488 Hom.: 14300 Cov.: 31 AF XY: 0.426 AC XY: 31565 AN XY: 74036

African (AFR) AF: 0.468 AC: 19346 AN: 41332

American (AMR) AF: 0.314 AC: 4787 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1582 AN: 3464

East Asian (EAS) AF: 0.478 AC: 2430 AN: 5088

South Asian (SAS) AF: 0.419 AC: 2000 AN: 4776

European-Finnish (FIN) AF: 0.417 AC: 4397 AN: 10534

Middle Eastern (MID) AF: 0.357 AC: 102 AN: 286

European-Non Finnish (NFE) AF: 0.432 AC: 29268 AN: 67776

Other (OTH) AF: 0.393 AC: 826 AN: 2100

Alfa AF: 0.420 Hom.: 1671

Bravo AF: 0.426

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.91
PhyloP100		-0.087
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: rs2070683; hg19: chr7-100779941;