rs2227694

Variant names:

• chr7-101136895-A-G
• rs2227694
• NM_000602.5:c.1088-106A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-101136895-A-G
• chr7-101136895-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22
• Publications: 12 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 -20 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 VariationId is 1253721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 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.1088-106A>G		intron	N/A	NP_000593.1	P05121-1
	SERPINE1	NM_001386460.1		c.1088-106A>G		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.1088-928A>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.1088-106A>G		intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.1112-106A>G		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.1103-106A>G		intron	N/A	ENSP00000620121.1

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

African (AFR) AF: 0.889 AC: 21347 AN: 24012

American (AMR) AF: 0.885 AC: 37284 AN: 42124

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 21243 AN: 22866

East Asian (EAS) AF: 0.967 AC: 35990 AN: 37216

South Asian (SAS) AF: 0.906 AC: 68694 AN: 75794

European-Finnish (FIN) AF: 0.802 AC: 39314 AN: 49026

Middle Eastern (MID) AF: 0.894 AC: 4333 AN: 4846

European-Non Finnish (NFE) AF: 0.853 AC: 571273 AN: 669770

Other (OTH) AF: 0.871 AC: 38461 AN: 44164

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

African (AFR) AF: 0.886 AC: 36741 AN: 41476

American (AMR) AF: 0.882 AC: 13471 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3215 AN: 3470

East Asian (EAS) AF: 0.954 AC: 4925 AN: 5162

South Asian (SAS) AF: 0.911 AC: 4380 AN: 4808

European-Finnish (FIN) AF: 0.801 AC: 8395 AN: 10476

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.851 AC: 57842 AN: 67950

Other (OTH) AF: 0.869 AC: 1830 AN: 2106

Alfa AF: 0.823 Hom.: 2954

Bravo AF: 0.874

Asia WGS AF: 0.928 AC: 3228 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-1.2
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: rs2227694; hg19: chr7-100780176; COSMIC: COSV56169705;