7-101123428-C-T

Variant names:

• chr7-101123428-C-T
• rs6465787
• ENST00000950058.1:c.-187+341C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000950058.1(SERPINE1):​c.-187+341C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 151,822 control chromosomes in the GnomAD database, including 950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (950 hom., cov: 31)
• Consequence: SERPINE1 ENST00000950058.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000950058.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000950058.1		c.-187+341C>T		intron	N/A	ENSP00000620117.1

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11448 AN: 151704 Hom.: 945 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0605

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

GnomAD4 genome AF: 0.0757 AC: 11486 AN: 151822 Hom.: 950 Cov.: 31 AF XY: 0.0762 AC XY: 5659 AN XY: 74228

African (AFR) AF: 0.212 AC: 8780 AN: 41348

American (AMR) AF: 0.0408 AC: 622 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3468

East Asian (EAS) AF: 0.0246 AC: 126 AN: 5130

South Asian (SAS) AF: 0.0152 AC: 73 AN: 4790

European-Finnish (FIN) AF: 0.0611 AC: 647 AN: 10586

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0150 AC: 1019 AN: 67946

Other (OTH) AF: 0.0598 AC: 126 AN: 2106

Alfa AF: 0.00705 Hom.: 0

Bravo AF: 0.0833

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6465787; hg19: chr7-100766709;