Variant 7-93886846-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006528.4(TFPI2):c.682C>T(p.Arg228Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,552,370 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

TFPI2
NM_006528.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004023999).

BP6

Variant 7-93886846-G-A is Benign according to our data. Variant chr7-93886846-G-A is described in ClinVar as [Benign]. Clinvar id is 712709.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TFPI2	NM_006528.4 linkuse as main transcript	c.682C>T	p.Arg228Trp	missense_variant	5/5	ENST00000222543.11
TFPI2	NM_001271003.2 linkuse as main transcript	c.649C>T	p.Arg217Trp	missense_variant	5/5
TFPI2	NM_001271004.2 linkuse as main transcript	c.*45C>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2	ENST00000222543.11 linkuse as main transcript	c.682C>T	p.Arg228Trp	missense_variant	5/5	1	NM_006528.4	P2	P48307-1
TFPI2	ENST00000650573.1 linkuse as main transcript	c.700C>T	p.Arg234Trp	missense_variant	5/5			A2
TFPI2	ENST00000451238.1 linkuse as main transcript	c.*45C>T		3_prime_UTR_variant	4/4	2
GNGT1	ENST00000455502.5 linkuse as main transcript	c.-12+297G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

646

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00109

AC:

211

AN:

193072

Hom.:

AF XY:

0.000825

AC XY:

AN XY:

106642

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.000785

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000183

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000517

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.000410

AC:

574

AN:

1400230

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

253

AN XY:

696050

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.0000409

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000448

Gnomad4 OTH exome

AF:

0.000932

GnomAD4 genome

AF:

0.00425

AC:

647

AN:

152140

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

319

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000689

Hom.:

Bravo

AF:

0.00481

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00139

AC:

169

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;.;.

REVEL

Benign

0.088

Sift

Benign

0.048

D;.;.

Sift4G

Uncertain

0.032

D;.;.

Polyphen

0.99

D;D;.

Vest4

0.17

MVP

0.76

MPC

0.16

ClinPred

0.0098

GERP RS

2.3

Varity_R

0.048

gMVP

0.38

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

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