Variant chr7-93889100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006528.4(TFPI2):c.395G>A(p.Arg132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,612,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

TFPI2
NM_006528.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008853614).

BP6

Variant 7-93889100-C-T is Benign according to our data. Variant chr7-93889100-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 730260.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TFPI2	NM_006528.4 linkuse as main transcript	c.395G>A	p.Arg132Gln	missense_variant	3/5	ENST00000222543.11
TFPI2	NM_001271003.2 linkuse as main transcript	c.362G>A	p.Arg121Gln	missense_variant	3/5
TFPI2	NM_001271004.2 linkuse as main transcript	c.395G>A	p.Arg132Gln	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2	ENST00000222543.11 linkuse as main transcript	c.395G>A	p.Arg132Gln	missense_variant	3/5	1	NM_006528.4	P2	P48307-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000381

AC:

AN:

249562

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.00527

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000179

AC:

261

AN:

1460486

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

726526

show subpopulations

Gnomad4 AFR exome

AF:

0.00578

Gnomad4 AMR exome

AF:

0.000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152212

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00537

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.00193

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

3.3

DANN

Benign

0.84

DEOGEN2

Benign

0.047

T;T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.018

MetaRNN

Benign

0.0089

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.38

N;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.15

N;.;N;.;.;.

REVEL

Benign

0.018

Sift

Benign

0.32

T;.;T;.;.;.

Sift4G

Benign

0.14

T;.;T;.;.;.

Polyphen

0.073

B;B;.;.;.;.

Vest4

0.12

MVP

0.26

MPC

0.15

ClinPred

0.0018

GERP RS

-3.7

Varity_R

0.020

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over