Variant 4-186084711-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003265.3(TLR3):c.2553C>T(p.Phe851Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,613,804 control chromosomes in the GnomAD database, including 1,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 540 hom., cov: 33)

Exomes 𝑓: 0.016 ( 674 hom. )

Consequence

TLR3
NM_003265.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.854

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-186084711-C-T is Benign according to our data. Variant chr4-186084711-C-T is described in ClinVar as [Benign]. Clinvar id is 470483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.854 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR3	NM_003265.3 link	c.2553C>T	p.Phe851Phe	synonymous_variant	5/5	ENST00000296795.8	NP_003256.1	O15455-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8 link	c.2553C>T	p.Phe851Phe	synonymous_variant	5/5	1	NM_003265.3	ENSP00000296795.3		O15455-1

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

8240

AN:

151996

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00718

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0446

GnomAD3 exomes

AF:

0.0227

AC:

5704

AN:

251314

Hom.:

250

AF XY:

0.0199

AC XY:

2707

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0219

Gnomad ASJ exome

AF:

0.0356

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0162

AC:

23683

AN:

1461690

Hom.:

674

Cov.:

AF XY:

0.0156

AC XY:

11308

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0343

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.00732

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0543

AC:

8262

AN:

152114

Hom.:

540

Cov.:

AF XY:

0.0527

AC XY:

3919

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00396

Gnomad4 FIN

AF:

0.00718

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0365

Hom.:

Bravo

AF:

0.0630

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0182

EpiControl

AF:

0.0192

ClinVar

Significance: 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.8

DANN

Benign

0.60

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