rs5743312

Positions:

• chr4-186079102-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003265.3(TLR3):​c.633+71C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,316,630 control chromosomes in the GnomAD database, including 15,542 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 0.14 (1594 hom., cov: 32)
  • Exomes 𝑓: 0.15 (13948 hom.)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR3	NM_003265.3	c.633+71C>T		intron_variant		ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.633+71C>T		intron_variant		1	NM_003265.3	ENSP00000296795.3
TLR3	ENST00000513189.1	n.633+71C>T		intron_variant		1		ENSP00000423386.1
TLR3	ENST00000698351.1	c.633+71C>T		intron_variant				ENSP00000513674.1
TLR3	ENST00000698352.1	n.*185+71C>T		intron_variant				ENSP00000513675.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21382 AN: 152092 Hom.: 1593 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.151 AC: 176226 AN: 1164420 Hom.: 13948 AF XY: 0.151 AC XY: 88949 AN XY: 587408

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.141 AC: 21399 AN: 152210 Hom.: 1594 Cov.: 32 AF XY: 0.141 AC XY: 10501 AN XY: 74418

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.149

Alfa AF: 0.148 Hom.: 840

Bravo AF: 0.141

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.073
DANN	Benign	0.22

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

Other links and lift over

dbSNP: rs5743312; hg19: chr4-187000256;