rs11536871
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The ENST00000394487.5(TLR4):c.-126A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,090,370 control chromosomes in the GnomAD database, including 755 homozygotes. 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 0.025 ( 82 hom., cov: 32)
Exomes 𝑓: 0.036 ( 673 hom. )
Consequence
TLR4
ENST00000394487.5 5_prime_UTR
ENST00000394487.5 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.540
Genes affected
TLR4 (HGNC:11850): (toll like receptor 4) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3840/152300) while in subpopulation NFE AF= 0.0378 (2568/68016). AF 95% confidence interval is 0.0365. There are 82 homozygotes in gnomad4. There are 1704 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 82 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TLR4 | NM_138554.5 | c.94-343A>C | intron_variant | ENST00000355622.8 | NP_612564.1 | |||
TLR4 | NM_003266.4 | c.-126A>C | 5_prime_UTR_variant | 2/4 | NP_003257.1 | |||
TLR4 | NM_138557.3 | c.-341+3655A>C | intron_variant | NP_612567.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TLR4 | ENST00000394487.5 | c.-126A>C | 5_prime_UTR_variant | 2/4 | 1 | ENSP00000377997 | ||||
TLR4 | ENST00000355622.8 | c.94-343A>C | intron_variant | 1 | NM_138554.5 | ENSP00000363089 | P1 | |||
TLR4 | ENST00000472304.2 | c.93+3655A>C | intron_variant | 1 | ENSP00000496429 | |||||
TLR4 | ENST00000490685.1 | n.24A>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0253 AC: 3845AN: 152182Hom.: 82 Cov.: 32
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GnomAD4 exome AF: 0.0363 AC: 34042AN: 938070Hom.: 673 Cov.: 30 AF XY: 0.0359 AC XY: 15808AN XY: 439860
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GnomAD4 genome AF: 0.0252 AC: 3840AN: 152300Hom.: 82 Cov.: 32 AF XY: 0.0229 AC XY: 1704AN XY: 74472
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at