rs2227667

chr7-101131468-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.506-407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,784 control chromosomes in the GnomAD database, including 5,324 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 0.25 (5324 hom., cov: 31)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE1	NM_000602.5	c.506-407A>G		intron_variant		ENST00000223095.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE1	ENST00000223095.5	c.506-407A>G		intron_variant		1	NM_000602.5	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38216 AN: 151666 Hom.: 5305 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.252 AC: 38263 AN: 151784 Hom.: 5324 Cov.: 31 AF XY: 0.259 AC XY: 19243 AN XY: 74160

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.299

Alfa AF: 0.231 Hom.: 1043

Bravo AF: 0.267

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.54
Dann	Benign	0.39

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: rs2227667; hg19: chr7-100774749;