rs10025405

Variant names:

• chr4-186085652-A-G
• rs10025405
• NM_003265.3:c.*779A>G

Variant summary

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

The NM_003265.3(TLR3):​c.*779A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,940 control chromosomes in the GnomAD database, including 12,912 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 0.40 (12912 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TLR3 NM_003265.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 22 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.*779A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.*779A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_003265.3	ENSP00000296795.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61401 AN: 151822 Hom.: 12923 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.374

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.404 AC: 61404 AN: 151940 Hom.: 12912 Cov.: 32 AF XY: 0.413 AC XY: 30632 AN XY: 74252

African (AFR) AF: 0.293 AC: 12154 AN: 41460

American (AMR) AF: 0.418 AC: 6374 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2764 AN: 5146

South Asian (SAS) AF: 0.469 AC: 2252 AN: 4804

European-Finnish (FIN) AF: 0.547 AC: 5769 AN: 10542

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29721 AN: 67942

Other (OTH) AF: 0.373 AC: 787 AN: 2112

Alfa AF: 0.420 Hom.: 34634

Bravo AF: 0.391

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.24
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: rs10025405; hg19: chr4-187006806;