7-101136660-A-T

Position:

• chr7-101136660-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000602.5(SERPINE1):​c.1088-341A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,488 control chromosomes in the GnomAD database, including 14,300 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 0.43 (14300 hom., cov: 31)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.1088-341A>T		intron_variant		ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.1088-341A>T		intron_variant		1	NM_000602.5	ENSP00000223095	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65230 AN: 151374 Hom.: 14293 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.431 AC: 65256 AN: 151488 Hom.: 14300 Cov.: 31 AF XY: 0.426 AC XY: 31565 AN XY: 74036

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.393

Alfa AF: 0.420 Hom.: 1671

Bravo AF: 0.426

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.91

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: rs2070683; hg19: chr7-100779941;