rs1519312

Variant names:

• chr4-186087690-G-A
• rs1519312
• NM_003265.3:c.*2817G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-186087690-G-A
• chr4-186087690-G-C

Variant summary

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

The NM_003265.3(TLR3):​c.*2817G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,020 control chromosomes in the GnomAD database, including 30,826 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 0.63 (30826 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TLR3 NM_003265.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.*2817G>A		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.*2817G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_003265.3	ENSP00000296795.3

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96392 AN: 151902 Hom.: 30798 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.653

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: 0.635 AC: 96468 AN: 152020 Hom.: 30826 Cov.: 32 AF XY: 0.635 AC XY: 47219 AN XY: 74332

African (AFR) AF: 0.642 AC: 26633 AN: 41458

American (AMR) AF: 0.707 AC: 10810 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3468

East Asian (EAS) AF: 0.683 AC: 3532 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2732 AN: 4822

European-Finnish (FIN) AF: 0.620 AC: 6535 AN: 10546

Middle Eastern (MID) AF: 0.653 AC: 188 AN: 288

European-Non Finnish (NFE) AF: 0.622 AC: 42245 AN: 67964

Other (OTH) AF: 0.656 AC: 1386 AN: 2112

Alfa AF: 0.634 Hom.: 26587

Bravo AF: 0.643

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.29
PhyloP100		0.17
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: rs1519312; hg19: chr4-187008844;