chr7-101123322-A-G

Variant names:

• chr7-101123322-A-G
• rs6950982
• ENST00000950058.1:c.-187+235A>G

Variant summary

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

The ENST00000950058.1(SERPINE1):​c.-187+235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,108 control chromosomes in the GnomAD database, including 3,428 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 0.19 (3428 hom., cov: 31)
• Consequence: SERPINE1 ENST00000950058.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000950058.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000950058.1		c.-187+235A>G		intron	N/A	ENSP00000620117.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28378 AN: 151988 Hom.: 3418 Cov.: 31

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.187 AC: 28398 AN: 152108 Hom.: 3428 Cov.: 31 AF XY: 0.192 AC XY: 14309 AN XY: 74362

African (AFR) AF: 0.0637 AC: 2647 AN: 41530

American (AMR) AF: 0.340 AC: 5171 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.153 AC: 794 AN: 5178

South Asian (SAS) AF: 0.181 AC: 873 AN: 4822

European-Finnish (FIN) AF: 0.283 AC: 2991 AN: 10584

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14649 AN: 67988

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.209 Hom.: 11781

Bravo AF: 0.184

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6950982; hg19: chr7-100766603;