7-101132405-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.700+336G>T		intron_variant	Intron 4 of 8	ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.700+336G>T		intron_variant	Intron 4 of 8	1	NM_000602.5	ENSP00000223095.4

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

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0947

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.124

Alfa AF: 0.123 Hom.: 1689

Bravo AF: 0.0992

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.85

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: rs2227672; hg19: chr7-100775686;