rs11178

Positions:

• chr7-101137803-T-C

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.*361T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 424,856 control chromosomes in the GnomAD database, including 40,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14872 hom., cov: 33)
  • Exomes 𝑓: 0.43 (25416 hom.)
• Consequence: SERPINE1 NM_000602.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.11

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=-0.82).
• BP6: Variant 7-101137803-T-C is Benign according to our data. Variant chr7-101137803-T-C is described in ClinVar as [Benign]. Clinvar id is 358316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE1	NM_000602.5	c.*361T>C		3_prime_UTR_variant	9/9	ENST00000223095.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE1	ENST00000223095.5	c.*361T>C		3_prime_UTR_variant	9/9	1	NM_000602.5	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66505 AN: 152028 Hom.: 14864 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.428 AC: 116682 AN: 272710 Hom.: 25416 Cov.: 0 AF XY: 0.426 AC XY: 61940 AN XY: 145510

Gnomad4 AFR exome AF: 0.492

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.437 AC: 66534 AN: 152146 Hom.: 14872 Cov.: 33 AF XY: 0.433 AC XY: 32199 AN XY: 74380

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.396

Alfa AF: 0.426 Hom.: 6150

Bravo AF: 0.435

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital plasminogen activator inhibitor type 1 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

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	-0.82
CADD	Benign	0.0080
DANN	Benign	0.48

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: rs11178; hg19: chr7-100781084; COSMIC: COSV99776894;