rs7668666

Variant names:

• chr4-186080138-C-A
• rs7668666
• NM_003265.3:c.633+1107C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-186080138-C-A
• chr4-186080138-C-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+1107C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,020 control chromosomes in the GnomAD database, including 4,346 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 0.23 (4346 hom., cov: 32)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 26 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 = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.633+1107C>A		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+1107C>A		intron_variant	Intron 3 of 4	1	NM_003265.3	ENSP00000296795.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34622 AN: 151902 Hom.: 4350 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34625 AN: 152020 Hom.: 4346 Cov.: 32 AF XY: 0.230 AC XY: 17123 AN XY: 74310

African (AFR) AF: 0.122 AC: 5071 AN: 41488

American (AMR) AF: 0.276 AC: 4211 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1734 AN: 5176

South Asian (SAS) AF: 0.271 AC: 1299 AN: 4800

European-Finnish (FIN) AF: 0.249 AC: 2630 AN: 10546

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18043 AN: 67956

Other (OTH) AF: 0.238 AC: 501 AN: 2108

Alfa AF: 0.239 Hom.: 2902

Bravo AF: 0.228

Asia WGS AF: 0.283 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7668666; hg19: chr4-187001292;