rs3775292

Variant names:

• chr4-186081871-C-G
• rs3775292
• ENST00000512264.1:c.-647C>G

Variant summary

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

The ENST00000512264.1(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 ENST00000512264.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 36 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512264.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR3	NM_003265.3	MANE Select	c.634-449C>G		intron	N/A	NP_003256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR3	ENST00000512264.1	TSL:1	c.-647C>G		5_prime_UTR	Exon 1 of 2	ENSP00000513668.1
	TLR3	ENST00000296795.8	TSL:1 MANE Select	c.634-449C>G		intron	N/A	ENSP00000296795.3
	TLR3	ENST00000513189.1	TSL:1	n.634-449C>G		intron	N/A	ENSP00000423386.1

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

African (AFR) AF: 0.861 AC: 205 AN: 238

American (AMR) AF: 0.852 AC: 1912 AN: 2244

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 170 AN: 266

East Asian (EAS) AF: 0.883 AC: 728 AN: 824

South Asian (SAS) AF: 0.687 AC: 1183 AN: 1722

European-Finnish (FIN) AF: 0.878 AC: 381 AN: 434

Middle Eastern (MID) AF: 0.783 AC: 36 AN: 46

European-Non Finnish (NFE) AF: 0.779 AC: 8525 AN: 10948

Other (OTH) 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

African (AFR) AF: 0.861 AC: 35718 AN: 41470

American (AMR) AF: 0.847 AC: 12938 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.877 AC: 4519 AN: 5150

South Asian (SAS) AF: 0.745 AC: 3582 AN: 4810

European-Finnish (FIN) AF: 0.907 AC: 9574 AN: 10560

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53888 AN: 67978

Other (OTH) AF: 0.785 AC: 1658 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.28
PromoterAI		-0.054	Neutral
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: rs3775292; hg19: chr4-187003025;