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GeneBe

rs35111588

chr4-186083390-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003265.3(TLR3):c.1704C>T(p.Asn568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00923 in 1,614,106 control chromosomes in the GnomAD database, including 1,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 603 hom., cov: 32)
Exomes 𝑓: 0.0051 ( 504 hom. )

Consequence

TLR3
NM_003265.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.389
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-186083390-C-T is Benign according to our data. Variant chr4-186083390-C-T is described in ClinVar as [Benign]. Clinvar id is 470478.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.389 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR3NM_003265.3 linkuse as main transcriptc.1704C>T p.Asn568= synonymous_variant 4/5 ENST00000296795.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR3ENST00000296795.8 linkuse as main transcriptc.1704C>T p.Asn568= synonymous_variant 4/51 NM_003265.3 P1O15455-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0490
AC:
7450
AN:
152100
Hom.:
602
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0176
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000794
Gnomad OTH
AF:
0.0368
GnomAD3 exomes
AF:
0.0128
AC:
3224
AN:
251316
Hom.:
255
AF XY:
0.00931
AC XY:
1265
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.172
Gnomad AMR exome
AF:
0.00882
Gnomad ASJ exome
AF:
0.000695
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000581
Gnomad OTH exome
AF:
0.00603
GnomAD4 exome
AF:
0.00507
AC:
7418
AN:
1461888
Hom.:
504
Cov.:
36
AF XY:
0.00441
AC XY:
3207
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.165
Gnomad4 AMR exome
AF:
0.0109
Gnomad4 ASJ exome
AF:
0.00103
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000394
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000500
Gnomad4 OTH exome
AF:
0.0117
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0491
AC:
7475
AN:
152218
Hom.:
603
Cov.:
32
AF XY:
0.0471
AC XY:
3504
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.170
Gnomad4 AMR
AF:
0.0176
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000794
Gnomad4 OTH
AF:
0.0365
Alfa
AF:
0.0294
Hom.:
161
Bravo
AF:
0.0552
Asia WGS
AF:
0.0120
AC:
41
AN:
3478
EpiCase
AF:
0.000981
EpiControl
AF:
0.000771

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.2
Dann
Benign
0.63

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: rs35111588; hg19: chr4-187004544; API