rs2227683

Positions:

• chr7-101133355-G-A
• chr7-101133355-G-T

Variant summary

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

The NM_000602.5(SERPINE1):​c.701-340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,946 control chromosomes in the GnomAD database, including 2,122 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 0.15 (2122 hom., cov: 32)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE1	NM_000602.5	c.701-340G>A		intron_variant		ENST00000223095.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE1	ENST00000223095.5	c.701-340G>A		intron_variant		1	NM_000602.5	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22419 AN: 151826 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.148 AC: 22417 AN: 151946 Hom.: 2122 Cov.: 32 AF XY: 0.144 AC XY: 10725 AN XY: 74248

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.152

Alfa AF: 0.170 Hom.: 293

Bravo AF: 0.139

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.52

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: rs2227683; hg19: chr7-100776636; COSMIC: COSV56171773;