rs3775292

Variant names:

• chr4-186081871-C-G
• rs3775292
• ENST00000512264:c.-647C>G

Variant summary

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

The ENST00000512264(TLR3):​c.-647C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 169,560 control chromosomes in the GnomAD database, including 57,248 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 0.82 (51758 hom., cov: 30)
  • Exomes 𝑓: 0.79 (5490 hom.)
• Consequence: TLR3 ENST00000512264 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.634-449C>G		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.634-449C>G		intron_variant	Intron 3 of 4	1	NM_003265.3	ENSP00000296795.3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125073 AN: 151920 Hom.: 51711 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.785

GnomAD4 exome AF: 0.786 AC: 13767 AN: 17522 Hom.: 5490 Cov.: 0 AF XY: 0.783 AC XY: 7436 AN XY: 9500

Gnomad4 AFR exome AF: 0.861 AC: 205 AN: 238

Gnomad4 AMR exome AF: 0.852 AC: 1912 AN: 2244

Gnomad4 ASJ exome AF: 0.639 AC: 170 AN: 266

Gnomad4 EAS exome AF: 0.883 AC: 728 AN: 824

Gnomad4 SAS exome AF: 0.687 AC: 1183 AN: 1722

Gnomad4 FIN exome AF: 0.878 AC: 381 AN: 434

Gnomad4 NFE exome AF: 0.779 AC: 8525 AN: 10948

Gnomad4 Remaining exome AF: 0.784 AC: 627 AN: 800

GnomAD4 genome AF: 0.823 AC: 125178 AN: 152038 Hom.: 51758 Cov.: 30 AF XY: 0.827 AC XY: 61421 AN XY: 74298

Gnomad4 AFR AF: 0.861 AC: 0.861297 AN: 0.861297

Gnomad4 AMR AF: 0.847 AC: 0.846506 AN: 0.846506

Gnomad4 ASJ AF: 0.678 AC: 0.677522 AN: 0.677522

Gnomad4 EAS AF: 0.877 AC: 0.877476 AN: 0.877476

Gnomad4 SAS AF: 0.745 AC: 0.744699 AN: 0.744699

Gnomad4 FIN AF: 0.907 AC: 0.906629 AN: 0.906629

Gnomad4 NFE AF: 0.793 AC: 0.792727 AN: 0.792727

Gnomad4 OTH AF: 0.785 AC: 0.785038 AN: 0.785038

Alfa AF: 0.815 Hom.: 6304

Bravo AF: 0.822

Asia WGS AF: 0.814 AC: 2833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.50
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

Publications

LitVar

Other links and lift over

dbSNP: rs3775292; hg19: chr4-187003025;