7-101130178-T-C

Position:

• chr7-101130178-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000602.5(SERPINE1):​c.272-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 146,298 control chromosomes in the GnomAD database, including 55,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (55096 hom., cov: 23)
• Consequence: SERPINE1 NM_000602.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-101130178-T-C is Benign according to our data. Variant chr7-101130178-T-C is described in ClinVar as [Benign]. Clinvar id is 1244356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE1	NM_000602.5	c.272-243T>C		intron_variant		ENST00000223095.5	NP_000593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE1	ENST00000223095.5	c.272-243T>C		intron_variant		1	NM_000602.5	ENSP00000223095.4

Frequencies

GnomAD3 genomes AF: 0.867 AC: 126813 AN: 146210 Hom.: 55065 Cov.: 23

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.867 AC: 126887 AN: 146298 Hom.: 55096 Cov.: 23 AF XY: 0.867 AC XY: 61363 AN XY: 70792

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.870

Alfa AF: 0.857 Hom.: 11619

Bravo AF: 0.874

Asia WGS AF: 0.926 AC: 3221 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.87

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: rs2227657; hg19: chr7-100773459;