rs2227683

Variant names:

• chr7-101133355-G-A
• rs2227683
• NM_000602.5:c.701-340G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101133355-G-A
• chr7-101133355-G-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.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
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 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.701-340G>A		intron	N/A	NP_000593.1	P05121-1
	SERPINE1	NM_001386460.1		c.701-340G>A		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.701-340G>A		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.701-340G>A		intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.725-340G>A		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.701-340G>A		intron	N/A	ENSP00000620121.1

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

African (AFR) AF: 0.0582 AC: 2412 AN: 41450

American (AMR) AF: 0.142 AC: 2160 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5176

South Asian (SAS) AF: 0.117 AC: 565 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2126 AN: 10526

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13948 AN: 67968

Other (OTH) AF: 0.152 AC: 319 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.54
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: rs2227683; hg19: chr7-100776636; COSMIC: COSV56171773;