rs4986790
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_138554.5(TLR4):c.896A>G(p.Asp299Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,613,856 control chromosomes in the GnomAD database, including 3,677 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_138554.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TLR4 | NM_138554.5 | c.896A>G | p.Asp299Gly | missense_variant | Exon 3 of 3 | ENST00000355622.8 | NP_612564.1 | |
TLR4 | NM_003266.4 | c.776A>G | p.Asp259Gly | missense_variant | Exon 4 of 4 | NP_003257.1 | ||
TLR4 | NM_138557.3 | c.296A>G | p.Asp99Gly | missense_variant | Exon 2 of 2 | NP_612567.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TLR4 | ENST00000355622.8 | c.896A>G | p.Asp299Gly | missense_variant | Exon 3 of 3 | 1 | NM_138554.5 | ENSP00000363089.5 | ||
ENSG00000285082 | ENST00000697666.1 | c.140+4295A>G | intron_variant | Intron 3 of 4 | ENSP00000513391.1 |
Frequencies
GnomAD3 genomes AF: 0.0660 AC: 10044AN: 152074Hom.: 378 Cov.: 32
GnomAD3 exomes AF: 0.0605 AC: 15187AN: 250890Hom.: 584 AF XY: 0.0629 AC XY: 8525AN XY: 135586
GnomAD4 exome AF: 0.0621 AC: 90797AN: 1461664Hom.: 3299 Cov.: 32 AF XY: 0.0632 AC XY: 45973AN XY: 727140
GnomAD4 genome AF: 0.0660 AC: 10042AN: 152192Hom.: 378 Cov.: 32 AF XY: 0.0684 AC XY: 5088AN XY: 74394
ClinVar
Submissions by phenotype
COPD, severe early onset Pathogenic:1
Allele associated with the development of COPD secondary to tobacco smoke -
Susceptibility to severe coronavirus disease (COVID-19) Uncertain:1
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TLR4 POLYMORPHISM Benign:1
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not provided Benign:1
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Pericementitis Benign:1
In an exploratory population (N=570, 186 cases/ 384 controls), rs4986790 demonstrated a significant protective effect for the phenotype of chronic periodontitis [OR 0.3315, CI 0.14-0.75, p-value 0.005] . The association analysis combining the exploratory and three independent validation populations (N=1410; 528 cases and 882 controls) demonstrated a significant protective effect of the polymorphic allele for the phenotype ‘susceptibility for inflammatory alveolar bone resorption’ [OR 0.57, CI 0.38-0.85, p-value 0.005]. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at