dbSNP rs4264: TFPI2:c.*55G>T (chr7-93886765-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006528.4(TFPI2):c.*55G>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 0.0000152 in 1,120,570 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TFPI2
NM_006528.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.124

Publications

11 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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	Effect	Exon Rank	Protein	UniProt
TFPI2	NM_006528.4	MANE Select	c.*55G>T	3_prime_UTR	Exon 5 of 5	NP_006519.1	P48307-1
TFPI2	NM_001271003.2		c.*55G>T	3_prime_UTR	Exon 5 of 5	NP_001257932.1	P48307-2
TFPI2	NM_001271004.2		c.*126G>T	3_prime_UTR	Exon 5 of 5	NP_001257933.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.*55G>T	3_prime_UTR	Exon 5 of 5	ENSP00000222543.5	P48307-1
TFPI2	ENST00000650573.1		c.*55G>T	3_prime_UTR	Exon 5 of 5	ENSP00000497131.1	A0A3B3IS67
TFPI2	ENST00000898459.1		c.*55G>T	3_prime_UTR	Exon 4 of 4	ENSP00000568518.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

968516

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

497962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19184

American (AMR)

AF:

0.00

AC:

AN:

21536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20820

East Asian (EAS)

AF:

0.00

AC:

AN:

31124

South Asian (SAS)

AF:

0.00

AC:

AN:

59102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4612

European-Non Finnish (NFE)

AF:

0.0000221

AC:

AN:

723782

Other (OTH)

AF:

0.00

AC:

AN:

43354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.87

(source)

DANN

Benign

0.51

PhyloP100

-0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over