rs913930

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138554.5(TLR4):​c.*7083G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,116 control chromosomes in the GnomAD database, including 41,391 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 0.73 ( 41391 hom., cov: 33)
Failed GnomAD Quality Control

Consequence

TLR4
NM_138554.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.623

Publications

33 publications found
Variant links:
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLR4NM_138554.5 linkc.*7083G>A 3_prime_UTR_variant Exon 3 of 3 ENST00000355622.8 NP_612564.1 O00206-1
TLR4NM_003266.4 linkc.*7083G>A 3_prime_UTR_variant Exon 4 of 4 NP_003257.1 O00206-2
TLR4NM_138557.3 linkc.*7083G>A 3_prime_UTR_variant Exon 2 of 2 NP_612567.1 O00206-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLR4ENST00000355622.8 linkc.*7083G>A 3_prime_UTR_variant Exon 3 of 3 1 NM_138554.5 ENSP00000363089.5 O00206-1
ENSG00000285082ENST00000697666.1 linkc.140+13002G>A intron_variant Intron 3 of 4 ENSP00000513391.1 A0A8V8TMK6

Frequencies

GnomAD3 genomes
AF:
0.728
AC:
110716
AN:
151998
Hom.:
41321
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.868
Gnomad AMI
AF:
0.616
Gnomad AMR
AF:
0.728
Gnomad ASJ
AF:
0.687
Gnomad EAS
AF:
0.987
Gnomad SAS
AF:
0.772
Gnomad FIN
AF:
0.594
Gnomad MID
AF:
0.576
Gnomad NFE
AF:
0.646
Gnomad OTH
AF:
0.707
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AC:
0
AN:
0
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome
AF:
0.729
AC:
110847
AN:
152116
Hom.:
41391
Cov.:
33
AF XY:
0.730
AC XY:
54259
AN XY:
74346
show subpopulations
African (AFR)
AF:
0.868
AC:
36086
AN:
41550
American (AMR)
AF:
0.728
AC:
11117
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.687
AC:
2386
AN:
3472
East Asian (EAS)
AF:
0.987
AC:
5122
AN:
5188
South Asian (SAS)
AF:
0.772
AC:
3720
AN:
4818
European-Finnish (FIN)
AF:
0.594
AC:
6259
AN:
10538
Middle Eastern (MID)
AF:
0.596
AC:
174
AN:
292
European-Non Finnish (NFE)
AF:
0.646
AC:
43924
AN:
67966
Other (OTH)
AF:
0.710
AC:
1497
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1471
2942
4413
5884
7355
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
828
1656
2484
3312
4140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.672
Hom.:
62821
Bravo
AF:
0.742
Asia WGS
AF:
0.884
AC:
3071
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
5.4
DANN
Benign
0.62
PhyloP100
0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs913930; hg19: chr9-120484009; API