rs2227694

chr7-101136895-A-Gchr7-101136895-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000602.5(SERPINE1):c.1088-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,121,740 control chromosomes in the GnomAD database, including 419,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57240 hom., cov: 31)
  • Exomes 𝑓: 0.86 (362598 hom.)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-101136895-A-G is Benign according to our data. Variant chr7-101136895-A-G is described in ClinVar as [Benign]. Clinvar id is 1253721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE1	NM_000602.5	c.1088-106A>G		intron_variant		ENST00000223095.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE1	ENST00000223095.5	c.1088-106A>G		intron_variant		1	NM_000602.5	P1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131765 AN: 151798 Hom.: 57199 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.868

GnomAD4 exome AF: 0.864 AC: 837939 AN: 969818 Hom.: 362598 AF XY: 0.865 AC XY: 435433 AN XY: 503230

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.906

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.868 AC: 131865 AN: 151922 Hom.: 57240 Cov.: 31 AF XY: 0.867 AC XY: 64388 AN XY: 74260

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.869

Alfa AF: 0.823 Hom.: 2954

Bravo AF: 0.874

Asia WGS AF: 0.928 AC: 3228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227694; hg19: chr7-100780176; COSMIC: COSV56169705;