rs1050813

Variant names:

• chr7-101138334-G-A
• rs1050813
• NM_000602.5:c.*892G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101138334-G-A
• chr7-101138334-G-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.*892G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,984 control chromosomes in the GnomAD database, including 2,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2058 hom., cov: 32)
  • Exomes 𝑓: 0.17 (18 hom.)
• Consequence: SERPINE1 NM_000602.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 29 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-101138334-G-A is Benign according to our data. Variant chr7-101138334-G-A is described in ClinVar as Benign. ClinVar VariationId is 358323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.*892G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.*892G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_000602.5	ENSP00000223095.4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21523 AN: 151998 Hom.: 2060 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.174 AC: 151 AN: 866 Hom.: 18 Cov.: 0 AF XY: 0.198 AC XY: 94 AN XY: 474

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.129 AC: 43 AN: 334

European-Finnish (FIN) AF: 0.204 AC: 87 AN: 426

Middle Eastern (MID) AF: 0.250 AC: 3 AN: 12

European-Non Finnish (NFE) AF: 0.205 AC: 16 AN: 78

Other (OTH) AF: 0.125 AC: 2 AN: 16

GnomAD4 genome AF: 0.141 AC: 21521 AN: 152118 Hom.: 2058 Cov.: 32 AF XY: 0.139 AC XY: 10301 AN XY: 74346

African (AFR) AF: 0.0407 AC: 1690 AN: 41486

American (AMR) AF: 0.137 AC: 2098 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5176

South Asian (SAS) AF: 0.114 AC: 548 AN: 4828

European-Finnish (FIN) AF: 0.201 AC: 2126 AN: 10574

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13867 AN: 67988

Other (OTH) AF: 0.147 AC: 311 AN: 2110

Alfa AF: 0.179 Hom.: 5217

Bravo AF: 0.133

Asia WGS AF: 0.0590 AC: 209 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital plasminogen activator inhibitor type 1 deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.76
PhyloP100		1.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
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: rs1050813; hg19: chr7-100781615; COSMIC: COSV56169562;