rs11178

Variant names:

• chr7-101137803-T-C
• rs11178
• NM_000602.5:c.*361T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001386460.1(SERPINE1):​c.1185T>C​(p.Asp395Asp) variant causes a synonymous 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_001386460.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.11
• Publications: 28 publications found

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]

SERPINE1 Gene-Disease associations (from GenCC):

• congenital plasminogen activator inhibitor type 1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 358316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386460.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	NM_000602.5	MANE Select	c.*361T>C		3_prime_UTR	Exon 9 of 9	NP_000593.1
	SERPINE1	NM_001386460.1		c.1185T>C	p.Asp395Asp	synonymous	Exon 9 of 9	NP_001373389.1
	SERPINE1	NM_001386464.1		c.*452T>C		3_prime_UTR	Exon 9 of 9	NP_001373393.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000223095.5	TSL:1 MANE Select	c.*361T>C		3_prime_UTR	Exon 9 of 9	ENSP00000223095.4
	SERPINE1	ENST00000950060.1		c.*361T>C		3_prime_UTR	Exon 9 of 9	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.*361T>C		3_prime_UTR	Exon 9 of 9	ENSP00000620121.1

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

African (AFR) AF: 0.492 AC: 4088 AN: 8306

American (AMR) AF: 0.292 AC: 3862 AN: 13236

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 3637 AN: 7874

East Asian (EAS) AF: 0.509 AC: 7573 AN: 14878

South Asian (SAS) AF: 0.407 AC: 16140 AN: 39688

European-Finnish (FIN) AF: 0.440 AC: 5706 AN: 12960

Middle Eastern (MID) AF: 0.390 AC: 420 AN: 1078

European-Non Finnish (NFE) AF: 0.431 AC: 68851 AN: 159688

Other (OTH) AF: 0.427 AC: 6405 AN: 15002

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

African (AFR) AF: 0.491 AC: 20392 AN: 41518

American (AMR) AF: 0.317 AC: 4838 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2450 AN: 5170

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4467 AN: 10592

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29328 AN: 67978

Other (OTH) AF: 0.396 AC: 837 AN: 2112

Alfa AF: 0.426 Hom.: 7235

Bravo AF: 0.435

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital plasminogen activator inhibitor type 1 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0080
DANN	Benign	0.48
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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