rs11732384

chr4-186071735-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003265.3(TLR3):c.-8+2487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,050 control chromosomes in the GnomAD database, including 1,353 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 0.12 (1353 hom., cov: 33)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR3	NM_003265.3	c.-8+2487G>A		intron_variant		ENST00000296795.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR3	ENST00000296795.8	c.-8+2487G>A		intron_variant		1	NM_003265.3	P1
TLR3	ENST00000513189.1	c.-8+2487G>A		intron_variant		1
TLR3	ENST00000698351.1	c.-8+2487G>A		intron_variant
TLR3	ENST00000698352.1	c.-8+2487G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17587 AN: 151932 Hom.: 1354 Cov.: 33

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.116 AC: 17580 AN: 152050 Hom.: 1353 Cov.: 33 AF XY: 0.120 AC XY: 8884 AN XY: 74300

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.133 Hom.: 214

Bravo AF: 0.103

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.40
Dann	Benign	0.64

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: rs11732384; hg19: chr4-186992889;