4-186079167-G-T

Variant names:

• chr4-186079167-G-T
• rs1879026
• NM_003265.3:c.633+136G>T

Variant summary

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

The NM_003265.3(TLR3):​c.633+136G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 839,342 control chromosomes in the GnomAD database, including 15,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2080 hom., cov: 32)
  • Exomes 𝑓: 0.19 (13082 hom.)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 24 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.633+136G>T		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.633+136G>T		intron_variant	Intron 3 of 4	1	NM_003265.3	ENSP00000296795.3
TLR3	ENST00000513189.1	n.633+136G>T		intron_variant	Intron 3 of 4	1		ENSP00000423386.1
TLR3	ENST00000698351.1	c.633+136G>T		intron_variant	Intron 3 of 4			ENSP00000513674.1
TLR3	ENST00000698352.1	n.*185+136G>T		intron_variant	Intron 3 of 4			ENSP00000513675.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23568 AN: 151924 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.187 AC: 128838 AN: 687300 Hom.: 13082 AF XY: 0.190 AC XY: 67916 AN XY: 357104

African (AFR) AF: 0.0522 AC: 892 AN: 17104

American (AMR) AF: 0.214 AC: 5361 AN: 25074

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 3959 AN: 16764

East Asian (EAS) AF: 0.240 AC: 7738 AN: 32262

South Asian (SAS) AF: 0.239 AC: 12851 AN: 53664

European-Finnish (FIN) AF: 0.194 AC: 8122 AN: 41834

Middle Eastern (MID) AF: 0.227 AC: 558 AN: 2460

European-Non Finnish (NFE) AF: 0.179 AC: 83124 AN: 464156

Other (OTH) AF: 0.183 AC: 6233 AN: 33982

GnomAD4 genome AF: 0.155 AC: 23567 AN: 152042 Hom.: 2080 Cov.: 32 AF XY: 0.158 AC XY: 11761 AN XY: 74280

African (AFR) AF: 0.0550 AC: 2285 AN: 41518

American (AMR) AF: 0.193 AC: 2948 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1168 AN: 5146

South Asian (SAS) AF: 0.228 AC: 1092 AN: 4792

European-Finnish (FIN) AF: 0.203 AC: 2143 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12476 AN: 67976

Other (OTH) AF: 0.178 AC: 375 AN: 2108

Alfa AF: 0.162 Hom.: 1476

Bravo AF: 0.153

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.54
PhyloP100		-1.5
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: rs1879026; hg19: chr4-187000321;