rs7668666

chr4-186080138-C-Achr4-186080138-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
TLR3	NM_003265.3	c.633+1107C>A		intron_variant		ENST00000296795.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR3	ENST00000296795.8	c.633+1107C>A		intron_variant		1	NM_003265.3	P1

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.238

Alfa AF: 0.233 Hom.: 2048

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7668666; hg19: chr4-187001292;