chr7-101132927-A-G

Position:

• chr7-101132927-A-G

Variant summary

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

The NM_000602.5(SERPINE1):​c.701-768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,210 control chromosomes in the GnomAD database, including 5,754 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 0.26 (5754 hom., cov: 30)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.701-768A>G		intron_variant		ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.701-768A>G		intron_variant		1	NM_000602.5	ENSP00000223095	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39766 AN: 151092 Hom.: 5736 Cov.: 30

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.263 AC: 39816 AN: 151210 Hom.: 5754 Cov.: 30 AF XY: 0.270 AC XY: 19960 AN XY: 73864

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.302

Alfa AF: 0.235 Hom.: 537

Bravo AF: 0.279

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.70

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: rs2227674; hg19: chr7-100776208;