rs13126816

Positions:

• chr4-186073024-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.-7-3589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,168 control chromosomes in the GnomAD database, including 3,602 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 0.21 (3602 hom., cov: 33)
• Consequence: TLR3 NM_003265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR3	NM_003265.3	c.-7-3589G>A		intron_variant		ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.-7-3589G>A		intron_variant		1	NM_003265.3	ENSP00000296795	P1
TLR3	ENST00000513189.1	c.-7-3589G>A		intron_variant		1		ENSP00000423386
TLR3	ENST00000698351.1	c.-7-3589G>A		intron_variant				ENSP00000513674
TLR3	ENST00000698352.1	c.-7-3589G>A		intron_variant, NMD_transcript_variant				ENSP00000513675

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31506 AN: 152050 Hom.: 3599 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.207 AC: 31526 AN: 152168 Hom.: 3602 Cov.: 33 AF XY: 0.208 AC XY: 15479 AN XY: 74392

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.235

Alfa AF: 0.236 Hom.: 7392

Bravo AF: 0.203

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.71

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: rs13126816; hg19: chr4-186994178;