4-186070148-C-T

Variant names:

• chr4-186070148-C-T
• rs11730143
• NM_003265.3:c.-8+900C>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.-8+900C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,858 control chromosomes in the GnomAD database, including 1,412 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 (1412 hom., cov: 33)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 5 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=-0.88).
• 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 rank	MANE	Protein	UniProt
TLR3	NM_003265.3	c.-8+900C>T		intron_variant	Intron 1 of 4	ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.-8+900C>T		intron_variant	Intron 1 of 4	1	NM_003265.3	ENSP00000296795.3
TLR3	ENST00000513189.1	n.-8+900C>T		intron_variant	Intron 1 of 4	1		ENSP00000423386.1
TLR3	ENST00000698351.1	c.-8+900C>T		intron_variant	Intron 1 of 4			ENSP00000513674.1
TLR3	ENST00000698352.1	n.-8+900C>T		intron_variant	Intron 1 of 4			ENSP00000513675.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18626 AN: 151740 Hom.: 1413 Cov.: 33

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.123 AC: 18626 AN: 151858 Hom.: 1412 Cov.: 33 AF XY: 0.127 AC XY: 9389 AN XY: 74220

African (AFR) AF: 0.0562 AC: 2328 AN: 41432

American (AMR) AF: 0.108 AC: 1650 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5168

South Asian (SAS) AF: 0.104 AC: 501 AN: 4812

European-Finnish (FIN) AF: 0.236 AC: 2477 AN: 10486

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10128 AN: 67916

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0737 Hom.: 113

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.51
PhyloP100		0.24
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: rs11730143; hg19: chr4-186991302;