NM_000602.5:c.700+336G>T

Variant names:

• chr7-101132405-G-T
• rs2227672
• NM_000602.5:c.700+336G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000602.5(SERPINE1):​c.700+336G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,068 control chromosomes in the GnomAD database, including 926 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 0.10 (926 hom., cov: 30)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 25 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, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000602.5. 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.700+336G>T		intron	N/A	NP_000593.1	P05121-1
	SERPINE1	NM_001386460.1		c.700+336G>T		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.700+336G>T		intron	N/A	NP_001373390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000223095.5	TSL:1 MANE Select	c.700+336G>T		intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.724+336G>T		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.700+336G>T		intron	N/A	ENSP00000620121.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15345 AN: 151950 Hom.: 923 Cov.: 30

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.101 AC: 15349 AN: 152068 Hom.: 926 Cov.: 30 AF XY: 0.0997 AC XY: 7410 AN XY: 74316

African (AFR) AF: 0.0517 AC: 2144 AN: 41488

American (AMR) AF: 0.0917 AC: 1399 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3472

East Asian (EAS) AF: 0.0947 AC: 489 AN: 5166

South Asian (SAS) AF: 0.135 AC: 651 AN: 4810

European-Finnish (FIN) AF: 0.0720 AC: 760 AN: 10560

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8969 AN: 67992

Other (OTH) AF: 0.124 AC: 261 AN: 2110

Alfa AF: 0.121 Hom.: 2034

Bravo AF: 0.0992

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.85
PhyloP100		0.093
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: rs2227672; hg19: chr7-100775686;