7-101133650-G-T

Variant names:

• chr7-101133650-G-T
• rs2227684
• NM_000602.5:c.701-45G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000602.5(SERPINE1):​c.701-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,439,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• 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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.701-45G>T		intron	N/A	NP_000593.1	P05121-1
	SERPINE1	NM_001386460.1		c.701-45G>T		intron	N/A	NP_001373389.1
	SERPINE1	NM_001386461.1		c.701-45G>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.701-45G>T		intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.725-45G>T		intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.701-45G>T		intron	N/A	ENSP00000620121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000417 AC: 6 AN: 1439636 Hom.: 0 Cov.: 28 AF XY: 0.00000418 AC XY: 3 AN XY: 717434

African (AFR) AF: 0.0000303 AC: 1 AN: 32982

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000458 AC: 5 AN: 1091976

Other (OTH) AF: 0.00 AC: 0 AN: 59636

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 45711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.044
DANN	Benign	0.76
PhyloP100		-0.69

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2227684;

hg19: chr7-100776931;