4-186083063-C-T

Position:

chr4-186083063-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003265.3(TLR3):c.1377C>T(p.Phe459Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,800 control chromosomes in the GnomAD database, including 74,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5962 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68766 hom. )

Consequence

TLR3
NM_003265.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 0.944

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]

TLR3 links:

TLR3 (HGNC:):

TLR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 4-186083063-C-T is Benign according to our data. Variant chr4-186083063-C-T is described in ClinVar as [Benign]. Clinvar id is 403543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.944 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR3	NM_003265.3 linkuse as main transcript	c.1377C>T	p.Phe459Phe	synonymous_variant	4/5	ENST00000296795.8	NP_003256.1	O15455-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8 linkuse as main transcript	c.1377C>T	p.Phe459Phe	synonymous_variant	4/5	1	NM_003265.3	ENSP00000296795.3		O15455-1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41804

AN:

151866

Hom.:

5963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.302

AC:

75834

AN:

251196

Hom.:

11782

AF XY:

0.302

AC XY:

41066

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.305

AC:

445532

AN:

1461816

Hom.:

68766

Cov.:

AF XY:

0.305

AC XY:

221921

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.275

AC:

41827

AN:

151984

Hom.:

5962

Cov.:

AF XY:

0.278

AC XY:

20641

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.0892

Hom.:

6761

Bravo

AF:

0.274

Asia WGS

AF:

0.311

AC:

1079

AN:

3478

EpiCase

AF:

0.306

EpiControl

AF:

0.301

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2020	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.9

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over