chr7-93886846-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_006528.4(TFPI2):c.682C>T(p.Arg228Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,552,370 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 2 hom. )
Consequence
TFPI2
NM_006528.4 missense
NM_006528.4 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 0.0340
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.004023999).
BP6
Variant 7-93886846-G-A is Benign according to our data. Variant chr7-93886846-G-A is described in ClinVar as [Benign]. Clinvar id is 712709.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFPI2 | NM_006528.4 | c.682C>T | p.Arg228Trp | missense_variant | 5/5 | ENST00000222543.11 | |
TFPI2 | NM_001271003.2 | c.649C>T | p.Arg217Trp | missense_variant | 5/5 | ||
TFPI2 | NM_001271004.2 | c.*45C>T | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFPI2 | ENST00000222543.11 | c.682C>T | p.Arg228Trp | missense_variant | 5/5 | 1 | NM_006528.4 | P2 | |
TFPI2 | ENST00000650573.1 | c.700C>T | p.Arg234Trp | missense_variant | 5/5 | A2 | |||
TFPI2 | ENST00000451238.1 | c.*45C>T | 3_prime_UTR_variant | 4/4 | 2 | ||||
GNGT1 | ENST00000455502.5 | c.-12+297G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00425 AC: 646AN: 152022Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00109 AC: 211AN: 193072Hom.: 1 AF XY: 0.000825 AC XY: 88AN XY: 106642
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GnomAD4 exome AF: 0.000410 AC: 574AN: 1400230Hom.: 2 Cov.: 30 AF XY: 0.000363 AC XY: 253AN XY: 696050
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GnomAD4 genome AF: 0.00425 AC: 647AN: 152140Hom.: 5 Cov.: 32 AF XY: 0.00429 AC XY: 319AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
D;.;.
Sift4G
Uncertain
D;.;.
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at