Variant 2-187484906-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006287.6(TFPI):c.440C>A(p.Thr147Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,588,708 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 17 hom. )

Consequence

TFPI
NM_006287.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

TFPI (HGNC:11760): (tissue factor pathway inhibitor) This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

TFPI links:

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

CALCRL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006154537).

BP6

Variant 2-187484906-G-T is Benign according to our data. Variant chr2-187484906-G-T is described in ClinVar as [Benign]. Clinvar id is 775182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI	NM_006287.6 linkuse as main transcript	c.440C>A	p.Thr147Lys	missense_variant	5/8	ENST00000233156.9
CALCRL-AS1	XR_007087504.1 linkuse as main transcript	n.3420-14600G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI	ENST00000233156.9 linkuse as main transcript	c.440C>A	p.Thr147Lys	missense_variant	5/8	1	NM_006287.6	P1	P10646-1
CALCRL-AS1	ENST00000412276.6 linkuse as main transcript	n.190-14600G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

151728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000725

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00194

AC:

454

AN:

233666

Hom.:

AF XY:

0.00262

AC XY:

332

AN XY:

126728

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.000907

Gnomad ASJ exome

AF:

0.00256

Gnomad EAS exome

AF:

0.0000592

Gnomad SAS exome

AF:

0.0103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000736

GnomAD4 exome

AF:

0.00172

AC:

2473

AN:

1436862

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1474

AN XY:

713062

show subpopulations

Gnomad4 AFR exome

AF:

0.000124

Gnomad4 AMR exome

AF:

0.000905

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00115

AC:

174

AN:

151846

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000724

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.00404

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

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.35

T;T;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.077

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

.;T;T;.;T

MetaRNN

Benign

0.0062

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.8

D;D;D;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;D;T;T

Sift4G

Uncertain

0.0030

D;D;.;D;D

Polyphen

0.0040

B;B;.;B;B

Vest4

0.24

MVP

0.70

MPC

0.71

ClinPred

0.069

GERP RS

5.9

Varity_R

0.30

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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