chr1-223111371-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003268.6(TLR5):c.1661A>G(p.Asp554Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000207 in 1,614,194 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
TLR5
NM_003268.6 missense
NM_003268.6 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 3.71
Genes affected
TLR5 (HGNC:11851): (toll like receptor 5) This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]
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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=0.016951919).
BP6
?
Variant 1-223111371-T-C is Benign according to our data. Variant chr1-223111371-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 723575.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR5 | NM_003268.6 | c.1661A>G | p.Asp554Gly | missense_variant | 6/6 | ENST00000642603.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR5 | ENST00000642603.2 | c.1661A>G | p.Asp554Gly | missense_variant | 6/6 | NM_003268.6 | P1 | ||
TLR5 | ENST00000540964.5 | c.1661A>G | p.Asp554Gly | missense_variant | 4/4 | 5 | P1 | ||
TLR5 | ENST00000645434.1 | c.1661A>G | p.Asp554Gly | missense_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.00106 AC: 162AN: 152196Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000295 AC: 74AN: 251164Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135748
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GnomAD4 exome AF: 0.000117 AC: 171AN: 1461880Hom.: 0 Cov.: 36 AF XY: 0.000106 AC XY: 77AN XY: 727238
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GnomAD4 genome ? AF: 0.00107 AC: 163AN: 152314Hom.: 2 Cov.: 32 AF XY: 0.000980 AC XY: 73AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;.
REVEL
Benign
Sift
Uncertain
D;.;D;.
Sift4G
Uncertain
D;.;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
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