rs6956010

Variant names:

• chr7-101123754-G-A
• rs6956010
• ENST00000950058.1:c.-187+667G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101123754-G-A
• chr7-101123754-G-C

Variant summary

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

The ENST00000950058.1(SERPINE1):​c.-187+667G>A 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 151,914 control chromosomes in the GnomAD database, including 3,426 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 (3426 hom., cov: 31)
• Consequence: SERPINE1 ENST00000950058.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 7 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 (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+667G>A		intron	N/A	ENSP00000620117.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28350 AN: 151798 Hom.: 3416 Cov.: 31

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0487

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.187 AC: 28370 AN: 151914 Hom.: 3426 Cov.: 31 AF XY: 0.193 AC XY: 14291 AN XY: 74236

African (AFR) AF: 0.0637 AC: 2645 AN: 41500

American (AMR) AF: 0.340 AC: 5181 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3468

East Asian (EAS) AF: 0.154 AC: 792 AN: 5130

South Asian (SAS) AF: 0.181 AC: 871 AN: 4814

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10568

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

European-Non Finnish (NFE) AF: 0.215 AC: 14623 AN: 67890

Other (OTH) AF: 0.211 AC: 445 AN: 2108

Alfa AF: 0.189 Hom.: 1666

Bravo AF: 0.184

Asia WGS AF: 0.167 AC: 580 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	4.0
DANN	Benign	0.33
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs6956010; hg19: chr7-100767035;