rs3775292

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000512264(TLR3):​c.-647C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 169,560 control chromosomes in the GnomAD database, including 57,248 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 0.82 ( 51758 hom., cov: 30)
Exomes 𝑓: 0.79 ( 5490 hom. )

Consequence

TLR3
ENST00000512264 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLR3NM_003265.3 linkuse as main transcriptc.634-449C>G intron_variant ENST00000296795.8 NP_003256.1 O15455-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLR3ENST00000296795.8 linkuse as main transcriptc.634-449C>G intron_variant 1 NM_003265.3 ENSP00000296795.3 O15455-1

Frequencies

GnomAD3 genomes
AF:
0.823
AC:
125073
AN:
151920
Hom.:
51711
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.861
Gnomad AMI
AF:
0.809
Gnomad AMR
AF:
0.846
Gnomad ASJ
AF:
0.678
Gnomad EAS
AF:
0.877
Gnomad SAS
AF:
0.746
Gnomad FIN
AF:
0.907
Gnomad MID
AF:
0.737
Gnomad NFE
AF:
0.793
Gnomad OTH
AF:
0.785
GnomAD4 exome
AF:
0.786
AC:
13767
AN:
17522
Hom.:
5490
Cov.:
0
AF XY:
0.783
AC XY:
7436
AN XY:
9500
show subpopulations
Gnomad4 AFR exome
AF:
0.861
Gnomad4 AMR exome
AF:
0.852
Gnomad4 ASJ exome
AF:
0.639
Gnomad4 EAS exome
AF:
0.883
Gnomad4 SAS exome
AF:
0.687
Gnomad4 FIN exome
AF:
0.878
Gnomad4 NFE exome
AF:
0.779
Gnomad4 OTH exome
AF:
0.784
GnomAD4 genome
AF:
0.823
AC:
125178
AN:
152038
Hom.:
51758
Cov.:
30
AF XY:
0.827
AC XY:
61421
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.861
Gnomad4 AMR
AF:
0.847
Gnomad4 ASJ
AF:
0.678
Gnomad4 EAS
AF:
0.877
Gnomad4 SAS
AF:
0.745
Gnomad4 FIN
AF:
0.907
Gnomad4 NFE
AF:
0.793
Gnomad4 OTH
AF:
0.785
Alfa
AF:
0.815
Hom.:
6304
Bravo
AF:
0.822
Asia WGS
AF:
0.814
AC:
2833
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.6
DANN
Benign
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3775292; hg19: chr4-187003025; API