Genetic Variant TFPI2:p.Glu107Glu (chr7-93889174-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006528.4(TFPI2):c.321G>A(p.Glu107Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,609,900 control chromosomes in the GnomAD database, including 2,309 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 0.061 ( 451 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1858 hom. )

Consequence

TFPI2
NM_006528.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.691

Variant links:

Genes affected

TFPI2 (HGNC:11761): (tissue factor pathway inhibitor 2) This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

TFPI2 links:

GNGT1 (HGNC:4411): (G protein subunit gamma transducin 1) This gene encodes the gamma subunit of transducin, a guanine nucleotide-binding protein (G protein) that is found in rod outer segments. Transducin, also known as GMPase, mediates the activation of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase by rhodopsin. [provided by RefSeq, Jul 2016]

GNGT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-0.691 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI2	NM_006528.4 link	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5	ENST00000222543.11	NP_006519.1	P48307-1
TFPI2	NM_001271003.2 link	c.288G>A	p.Glu96Glu	synonymous_variant	Exon 3 of 5		NP_001257932.1	P48307-2
TFPI2	NM_001271004.2 link	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11 link	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5	1	NM_006528.4	ENSP00000222543.5		P48307-1

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

9251

AN:

152064

Hom.:

448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.0861

Gnomad FIN

AF:

0.0259

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0582

AC:

14366

AN:

246830

Hom.:

736

AF XY:

0.0546

AC XY:

7298

AN XY:

133556

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.0463

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.0727

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0209

Gnomad OTH exome

AF:

0.0482

GnomAD4 exome

AF:

0.0321

AC:

46851

AN:

1457718

Hom.:

1858

Cov.:

AF XY:

0.0329

AC XY:

23822

AN XY:

724760

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.0484

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.0740

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0401

GnomAD4 genome

AF:

0.0609

AC:

9271

AN:

152182

Hom.:

451

Cov.:

AF XY:

0.0637

AC XY:

4738

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.0858

Gnomad4 FIN

AF:

0.0259

Gnomad4 NFE

AF:

0.0193

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.0667

Asia WGS

AF:

0.166

AC:

578

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over