rs4833095
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003263.4(TLR1):c.743A>G(p.Asn248Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,238 control chromosomes in the GnomAD database, including 90,036 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
Genomes: 𝑓 0.44 ( 19255 hom., cov: 32)
Exomes 𝑓: 0.27 ( 70781 hom. )
Consequence
TLR1
NM_003263.4 missense
NM_003263.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.964
Genes affected
TLR1 (HGNC:11847): (toll like receptor 1) 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 (PAMPs) 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. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=2.6334178E-6).
BP6
?
Variant 4-38798089-T-C is Benign according to our data. Variant chr4-38798089-T-C is described in ClinVar as [Benign]. Clinvar id is 8361.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR1 | NM_003263.4 | c.743A>G | p.Asn248Ser | missense_variant | 4/4 | ENST00000308979.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR1 | ENST00000308979.7 | c.743A>G | p.Asn248Ser | missense_variant | 4/4 | 1 | NM_003263.4 | P1 | |
TLR1 | ENST00000502213.6 | c.743A>G | p.Asn248Ser | missense_variant | 3/3 | 1 | P1 | ||
TLR1 | ENST00000505744.5 | n.235+2768A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.436 AC: 66260AN: 152006Hom.: 19203 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.381 AC: 95308AN: 250080Hom.: 22422 AF XY: 0.374 AC XY: 50670AN XY: 135426
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GnomAD4 exome AF: 0.273 AC: 399521AN: 1461114Hom.: 70781 Cov.: 36 AF XY: 0.279 AC XY: 202717AN XY: 726712
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GnomAD4 genome ? AF: 0.436 AC: 66372AN: 152124Hom.: 19255 Cov.: 32 AF XY: 0.435 AC XY: 32398AN XY: 74396
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837
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954
ESP6500AA
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3424
ESP6500EA
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2141
ExAC
?
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47671
Asia WGS
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1960
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TLR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Leprosy, susceptibility to, 5 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 15, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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