rs143367024

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R228Q) has been classified as Uncertain significance.

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0340

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 712709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFPI2	NM_006528.4	MANE Select	c.682C>T	p.Arg228Trp	missense	Exon 5 of 5	NP_006519.1	P48307-1
TFPI2	NM_001271003.2		c.649C>T	p.Arg217Trp	missense	Exon 5 of 5	NP_001257932.1	P48307-2
TFPI2	NM_001271004.2		c.*45C>T		3_prime_UTR	Exon 5 of 5	NP_001257933.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.682C>T	p.Arg228Trp	missense	Exon 5 of 5	ENSP00000222543.5	P48307-1
TFPI2	ENST00000650573.1		c.700C>T	p.Arg234Trp	missense	Exon 5 of 5	ENSP00000497131.1	A0A3B3IS67
TFPI2	ENST00000898459.1		c.511C>T	p.Arg171Trp	missense	Exon 4 of 4	ENSP00000568518.1

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

GnomAD2 exomes

AF:

0.00109

AC:

211

AN:

193072

AF XY:

0.000825

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 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

African (AFR)

AF:

0.0143

AC:

417

AN:

29232

American (AMR)

AF:

0.00129

AC:

AN:

29398

Ashkenazi Jewish (ASJ)

AF:

0.0000409

AC:

AN:

24452

East Asian (EAS)

AF:

0.00

AC:

AN:

36448

South Asian (SAS)

AF:

0.000106

AC:

AN:

75444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47834

Middle Eastern (MID)

AF:

0.00125

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.0000448

AC:

AN:

1093858

Other (OTH)

AF:

0.000932

AC:

AN:

57950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00425

AC:

647

AN:

152140

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

319

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0146

AC:

606

AN:

41534

American (AMR)

AF:

0.00164

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67934

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00177

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.034

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.088

Sift

Benign

0.048

Sift4G

Uncertain

0.032

Polyphen

0.99

Vest4

0.17

MVP

0.76

MPC

0.16

ClinPred

0.0098

GERP RS

2.3

Varity_R

0.048

gMVP

0.38

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over