7-101130178-T-C

Variant names:

• chr7-101130178-T-C
• rs2227657
• NM_000602.5:c.272-243T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000223095.5(SERPINE1):​c.272-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 146,298 control chromosomes in the GnomAD database, including 55,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (55096 hom., cov: 23)
• Consequence: SERPINE1 ENST00000223095.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-101130178-T-C is Benign according to our data. Variant chr7-101130178-T-C is described in ClinVar as Benign. ClinVar VariationId is 1244356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000223095.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	NM_000602.5	MANE Select	c.272-243T>C		intron	N/A	NP_000593.1
	SERPINE1	NM_001386460.1		c.272-243T>C		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.272-243T>C		intron	N/A	NP_001373390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000223095.5	TSL:1 MANE Select	c.272-243T>C		intron	N/A	ENSP00000223095.4

Frequencies

GnomAD3 genomes AF: 0.867 AC: 126813 AN: 146210 Hom.: 55065 Cov.: 23

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.867 AC: 126887 AN: 146298 Hom.: 55096 Cov.: 23 AF XY: 0.867 AC XY: 61363 AN XY: 70792

African (AFR) AF: 0.885 AC: 34820 AN: 39352

American (AMR) AF: 0.881 AC: 12723 AN: 14436

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3205 AN: 3460

East Asian (EAS) AF: 0.951 AC: 4734 AN: 4976

South Asian (SAS) AF: 0.910 AC: 4270 AN: 4692

European-Finnish (FIN) AF: 0.793 AC: 6893 AN: 8696

Middle Eastern (MID) AF: 0.870 AC: 247 AN: 284

European-Non Finnish (NFE) AF: 0.851 AC: 57436 AN: 67480

Other (OTH) AF: 0.870 AC: 1758 AN: 2020

Alfa AF: 0.864 Hom.: 21445

Bravo AF: 0.874

Asia WGS AF: 0.926 AC: 3221 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.87
PhyloP100		-1.0
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: rs2227657; hg19: chr7-100773459;