rs1194865614

Variant names:

• chr7-101132065-CTA-C
• rs1194865614
• ENST00000223095.5:c.688_689delTA

Your query was ambiguous. Multiple possible variants found:

• chr7-101132065-CTA-C
• chr7-101132065-CTA-CTATA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000223095.5(SERPINE1):​c.688_689delTA​(p.Lys230fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SERPINE1 ENST00000223095.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.82
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-101132065-CTA-C is Pathogenic according to our data. Variant chr7-101132065-CTA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 13571.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.699_700delTA	p.Thr234fs	frameshift_variant, splice_region_variant	Exon 4 of 9	ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.688_689delTA	p.Lys230fs	frameshift_variant	Exon 4 of 9	1	NM_000602.5	ENSP00000223095.4

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital plasminogen activator inhibitor type 1 deficiency Pathogenic:1

Jul 01, 1997

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

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: rs1194865614; hg19: chr7-100775346;