rs10025405

chr4-186085652-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	UniProt
TLR3	NM_003265.3	c.*779A>G		3_prime_UTR_variant	5/5	ENST00000296795.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR3	ENST00000296795.8	c.*779A>G		3_prime_UTR_variant	5/5	1	NM_003265.3	P1
TLR3	ENST00000698354.1	c.*779A>G		3_prime_UTR_variant	3/3
TLR3	ENST00000698353.1	n.3369A>G		non_coding_transcript_exon_variant	3/3
TLR3	ENST00000698352.1	c.*3046A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5

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

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.373

Alfa AF: 0.421 Hom.: 21075

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

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: rs10025405; hg19: chr4-187006806;