dbSNP rs4271: TFPI2:c.*877A>T (chr7-93885943-T-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_006528.4(TFPI2):c.*877A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,132 control chromosomes in the GnomAD database, including 477 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 0.063 ( 477 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

TFPI2
NM_006528.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

6 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TFPI2	NM_006528.4 link	c.*877A>T	3_prime_UTR_variant	Exon 5 of 5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2 link	c.*877A>T	3_prime_UTR_variant	Exon 5 of 5		NP_001257932.1
TFPI2	NM_001271004.2 link	c.*948A>T	3_prime_UTR_variant	Exon 5 of 5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11 link	c.*877A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_006528.4	ENSP00000222543.5
GNGT1	ENST00000455502.5 link	c.-55-563T>A		intron_variant	Intron 1 of 3	2		ENSP00000395857.1

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9489

AN:

152014

Hom.:

471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0502

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.0863

Gnomad FIN

AF:

0.0252

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.0589

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0626

AC:

9524

AN:

152132

Hom.:

477

Cov.:

AF XY:

0.0655

AC XY:

4869

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.112

AC:

4661

AN:

41532

American (AMR)

AF:

0.110

AC:

1682

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0502

AC:

174

AN:

3464

East Asian (EAS)

AF:

0.166

AC:

860

AN:

5180

South Asian (SAS)

AF:

0.0860

AC:

415

AN:

4826

European-Finnish (FIN)

AF:

0.0252

AC:

267

AN:

10616

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0192

AC:

1305

AN:

67904

Other (OTH)

AF:

0.0588

AC:

124

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

439

879

1318

1758

2197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0391

Hom.:

Bravo

AF:

0.0685

Asia WGS

AF:

0.161

AC:

556

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

0.15

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over