rs2227684

Positions:

• chr7-101133650-G-A
• chr7-101133650-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000602.5(SERPINE1):​c.701-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,589,982 control chromosomes in the GnomAD database, including 147,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14595 hom., cov: 32)
  • Exomes 𝑓: 0.43 (132771 hom.)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.691

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-101133650-G-A is Benign according to our data. Variant chr7-101133650-G-A is described in ClinVar as [Benign]. Clinvar id is 1246591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE1	NM_000602.5	c.701-45G>A		intron_variant		ENST00000223095.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE1	ENST00000223095.5	c.701-45G>A		intron_variant		1	NM_000602.5	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65839 AN: 151916 Hom.: 14589 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.393

GnomAD3 exomes AF: 0.408 AC: 101733 AN: 249100 Hom.: 21314 AF XY: 0.412 AC XY: 55502 AN XY: 134806

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.459

Gnomad EAS exome AF: 0.461

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.427 AC: 613931 AN: 1437948 Hom.: 132771 Cov.: 28 AF XY: 0.427 AC XY: 305716 AN XY: 716650

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.433 AC: 65865 AN: 152034 Hom.: 14595 Cov.: 32 AF XY: 0.429 AC XY: 31867 AN XY: 74328

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.390

Alfa AF: 0.417 Hom.: 18798

Bravo AF: 0.430

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.064
DANN	Benign	0.77

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: rs2227684; hg19: chr7-100776931; COSMIC: COSV56169612;