Variant rs59740167 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006528.4(TFPI2):c.271+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,502,460 control chromosomes in the GnomAD database, including 2,046 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 0.061 ( 447 hom., cov: 33)

Exomes 𝑓: 0.030 ( 1599 hom. )

Consequence

TFPI2
NM_006528.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.721

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TFPI2	NM_006528.4 linkuse as main transcript	c.271+49G>A	intron_variant	ENST00000222543.11
TFPI2	NM_001271003.2 linkuse as main transcript	c.238+49G>A	intron_variant
TFPI2	NM_001271004.2 linkuse as main transcript	c.271+49G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2	ENST00000222543.11 linkuse as main transcript	c.271+49G>A		intron_variant		1	NM_006528.4	P2	P48307-1

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9293

AN:

152198

Hom.:

442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0567

AC:

9880

AN:

174344

Hom.:

470

AF XY:

0.0526

AC XY:

4952

AN XY:

94060

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0443

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.0750

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0302

AC:

40838

AN:

1350144

Hom.:

1599

Cov.:

AF XY:

0.0310

AC XY:

20473

AN XY:

661074

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0473

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.0743

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0392

GnomAD4 genome

AF:

0.0612

AC:

9322

AN:

152316

Hom.:

447

Cov.:

AF XY:

0.0637

AC XY:

4742

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.0857

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0367

Hom.:

Bravo

AF:

0.0672

Asia WGS

AF:

0.165

AC:

575

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.6

DANN

Benign

0.91

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over