rs4986791
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_138554(TLR4):c.1196C>T(p.Thr399Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152076 control chromosomes in the gnomAD Genomes database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.049 ( 250 hom., cov: 32)
Exomes 𝑓: 0.057 ( 537 hom. )
Consequence
TLR4
NM_138554 missense
NM_138554 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: -0.201
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0031039119).
BP6
?
Variant 9:117713324-C>T is Benign according to our data. Variant chr9-117713324-C-T is described in ClinVar as [Benign]. Clinvar id is 6661. Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-117713324-C-T is described in Lovd as [Likely_benign].
BA1
?
GnomAd highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR4 | NM_138554.5 | c.1196C>T | p.Thr399Ile | missense_variant | 3/3 | ENST00000355622.8 | |
TLR4 | NM_003266.4 | c.1076C>T | p.Thr359Ile | missense_variant | 4/4 | ||
TLR4 | NM_138557.3 | c.596C>T | p.Thr199Ile | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR4 | ENST00000355622.8 | c.1196C>T | p.Thr399Ile | missense_variant | 3/3 | 1 | NM_138554.5 | P1 | |
TLR4 | ENST00000394487.5 | c.1076C>T | p.Thr359Ile | missense_variant | 4/4 | 1 | |||
TLR4 | ENST00000472304.2 | c.*930C>T | 3_prime_UTR_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0494 AC: 7511AN: 152076Hom.: 250 Cov.: 32
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GnomAD3 exomes AF: 0.0566 AC: 14176AN: 250350Hom.: 537 AF XY: 0.0602 AC XY: 8143AN XY: 135366
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GnomAD4 exome AF: 0.0625 AC: 91406AN: 1461700Hom.: 3347 AF XY: 0.0636 AC XY: 46272AN XY: 727150
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189
ALSPAC
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217
ESP6500AA
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73
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538
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6681
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221
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
TLR4 POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 18, 2002 | - - |
not provided Other:1
not provided, no assertion provided | literature only | NEI Ophthalmic Genomics Laboratory, National Institutes of Health | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
A;A
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Benign
T;.;T
Polyphen
0.18
.;B;B
Vest4
MPC
0.12
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at