dbSNP rs3213739: TFPI:c.628+181A>C (chr2-187483943-T-G) – 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.628+181A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 554,962 control chromosomes in the GnomAD database, including 82,810 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 0.49 ( 19133 hom., cov: 32)

Exomes 𝑓: 0.56 ( 63677 hom. )

Consequence

TFPI
NM_006287.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

9 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI	NM_006287.6 link	c.628+181A>C		intron_variant	Intron 6 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.628+181A>C		intron_variant	Intron 6 of 7	1	NM_006287.6	ENSP00000233156.3		P10646-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74424

AN:

151614

Hom.:

19129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.557

AC:

224606

AN:

403230

Hom.:

63677

Cov.:

AF XY:

0.555

AC XY:

118188

AN XY:

212900

show subpopulations

African (AFR)

AF:

0.334

AC:

3140

AN:

9406

American (AMR)

AF:

0.479

AC:

5799

AN:

12106

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

7324

AN:

13120

East Asian (EAS)

AF:

0.693

AC:

18287

AN:

26404

South Asian (SAS)

AF:

0.537

AC:

16749

AN:

31206

European-Finnish (FIN)

AF:

0.558

AC:

17479

AN:

31328

Middle Eastern (MID)

AF:

0.427

AC:

843

AN:

1974

European-Non Finnish (NFE)

AF:

0.560

AC:

142399

AN:

254300

Other (OTH)

AF:

0.538

AC:

12586

AN:

23386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4563

9126

13690

18253

22816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.491

AC:

74445

AN:

151732

Hom.:

19133

Cov.:

AF XY:

0.490

AC XY:

36386

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.331

AC:

13718

AN:

41438

American (AMR)

AF:

0.468

AC:

7098

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1964

AN:

3464

East Asian (EAS)

AF:

0.660

AC:

3415

AN:

5172

South Asian (SAS)

AF:

0.542

AC:

2612

AN:

4816

European-Finnish (FIN)

AF:

0.560

AC:

5920

AN:

10576

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38069

AN:

67788

Other (OTH)

AF:

0.473

AC:

997

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1884

3768

5652

7536

9420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.503

Hom.:

3108

Bravo

AF:

0.479

Asia WGS

AF:

0.563

AC:

1960

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

(source)

DANN

Benign

0.43

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(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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rs3213739

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