dbSNP rs8176612: TFPI:c.536-202C>T (chr2-187484418-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006287.6(TFPI):c.536-202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 555,404 control chromosomes in the GnomAD database, including 647 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 0.037 ( 164 hom., cov: 32)

Exomes 𝑓: 0.043 ( 483 hom. )

Consequence

TFPI
NM_006287.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI	NM_006287.6 link	c.536-202C>T		intron_variant	Intron 5 of 7	ENST00000233156.9	NP_006278.1	P10646-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI	ENST00000233156.9 link	c.536-202C>T		intron_variant	Intron 5 of 7	1	NM_006287.6	ENSP00000233156.3		P10646-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5594

AN:

151728

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0737

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0565

Gnomad OTH

AF:

0.0537

GnomAD4 exome

AF:

0.0432

AC:

17419

AN:

403558

Hom.:

483

Cov.:

AF XY:

0.0418

AC XY:

8876

AN XY:

212204

show subpopulations

African (AFR)

AF:

0.0103

AC:

109

AN:

10602

American (AMR)

AF:

0.0303

AC:

406

AN:

13404

Ashkenazi Jewish (ASJ)

AF:

0.0660

AC:

842

AN:

12752

East Asian (EAS)

AF:

0.000247

AC:

AN:

28370

South Asian (SAS)

AF:

0.0100

AC:

336

AN:

33440

European-Finnish (FIN)

AF:

0.0225

AC:

626

AN:

27834

Middle Eastern (MID)

AF:

0.0717

AC:

130

AN:

1812

European-Non Finnish (NFE)

AF:

0.0554

AC:

13943

AN:

251454

Other (OTH)

AF:

0.0427

AC:

1020

AN:

23890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

779

1557

2336

3114

3893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0368

AC:

5591

AN:

151846

Hom.:

164

Cov.:

AF XY:

0.0348

AC XY:

2585

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.0108

AC:

450

AN:

41498

American (AMR)

AF:

0.0405

AC:

616

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.0737

AC:

255

AN:

3462

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00934

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0207

AC:

219

AN:

10594

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0565

AC:

3827

AN:

67794

Other (OTH)

AF:

0.0527

AC:

111

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

270

540

809

1079

1349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0425

Hom.:

Bravo

AF:

0.0360

Asia WGS

AF:

0.00463

AC:

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.083

(source)

DANN

Benign

0.29

PhyloP100

-1.0

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over