rs75290011
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_003265.3(TLR3):āc.727T>Cā(p.Leu243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0017 ( 0 hom., cov: 32)
Exomes š: 0.00020 ( 1 hom. )
Consequence
TLR3
NM_003265.3 synonymous
NM_003265.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.02
Genes affected
TLR3 (HGNC:11849): (toll like receptor 3) 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 receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 4-186082413-T-C is Benign according to our data. Variant chr4-186082413-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 470485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.02 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.727T>C | p.Leu243= | synonymous_variant | 4/5 | ENST00000296795.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.727T>C | p.Leu243= | synonymous_variant | 4/5 | 1 | NM_003265.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00173 AC: 263AN: 152072Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
263
AN:
152072
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000497 AC: 125AN: 251440Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135890
GnomAD3 exomes
AF:
AC:
125
AN:
251440
Hom.:
AF XY:
AC XY:
46
AN XY:
135890
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000198 AC: 289AN: 1461884Hom.: 1 Cov.: 37 AF XY: 0.000146 AC XY: 106AN XY: 727240
GnomAD4 exome
AF:
AC:
289
AN:
1461884
Hom.:
Cov.:
37
AF XY:
AC XY:
106
AN XY:
727240
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00174 AC: 265AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00164 AC XY: 122AN XY: 74406
GnomAD4 genome
?
AF:
AC:
265
AN:
152190
Hom.:
Cov.:
32
AF XY:
AC XY:
122
AN XY:
74406
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | TLR3: BP4, BP7 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at