rs59740167

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006528.4(TFPI2):​c.271+49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,350,356 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: not found (cov: 33)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

TFPI2
NM_006528.4 intron

Scores

2

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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFPI2NM_006528.4 linkc.271+49G>T intron_variant Intron 2 of 4 ENST00000222543.11 NP_006519.1 P48307-1
TFPI2NM_001271003.2 linkc.238+49G>T intron_variant Intron 2 of 4 NP_001257932.1 P48307-2
TFPI2NM_001271004.2 linkc.271+49G>T intron_variant Intron 2 of 4 NP_001257933.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFPI2ENST00000222543.11 linkc.271+49G>T intron_variant Intron 2 of 4 1 NM_006528.4 ENSP00000222543.5 P48307-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.41e-7
AC:
1
AN:
1350356
Hom.:
0
Cov.:
29
AF XY:
0.00000151
AC XY:
1
AN XY:
661182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
5.9
DANN
Benign
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-93519400; API