rs5743315

Variant names:

• chr4-186079262-C-A
• rs5743315
• NM_003265.3:c.633+231C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-186079262-C-A
• chr4-186079262-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003265.3(TLR3):​c.633+231C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 152,170 control chromosomes in the GnomAD database, including 224 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 0.038 (224 hom., cov: 32)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 83, susceptibility to viral infections

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.633+231C>A		intron_variant	Intron 3 of 4	ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.633+231C>A		intron_variant	Intron 3 of 4	1	NM_003265.3	ENSP00000296795.3
TLR3	ENST00000513189.1	n.633+231C>A		intron_variant	Intron 3 of 4	1		ENSP00000423386.1
TLR3	ENST00000698351.1	c.633+231C>A		intron_variant	Intron 3 of 4			ENSP00000513674.1
TLR3	ENST00000698352.1	n.*185+231C>A		intron_variant	Intron 3 of 4			ENSP00000513675.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5706 AN: 152052 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00726

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0375 AC: 5712 AN: 152170 Hom.: 224 Cov.: 32 AF XY: 0.0357 AC XY: 2655 AN XY: 74388

African (AFR) AF: 0.0965 AC: 4006 AN: 41508

American (AMR) AF: 0.0280 AC: 427 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4812

European-Finnish (FIN) AF: 0.00726 AC: 77 AN: 10600

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0136 AC: 922 AN: 68024

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.00278 Hom.: 0

Bravo AF: 0.0428

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743315; hg19: chr4-187000416;