chr4-186079221-G-C

Position:

• chr4-186079221-G-C

Variant summary

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

The ENST00000296795.8(TLR3):​c.633+190G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,932 control chromosomes in the GnomAD database, including 2,802 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 0.19 (2802 hom., cov: 32)
• Consequence: TLR3 ENST00000296795.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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 (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR3	NM_003265.3	c.633+190G>C		intron_variant		ENST00000296795.8	NP_003256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR3	ENST00000296795.8	c.633+190G>C		intron_variant		1	NM_003265.3	ENSP00000296795	P1
TLR3	ENST00000513189.1	c.633+190G>C		intron_variant		1		ENSP00000423386
TLR3	ENST00000698351.1	c.633+190G>C		intron_variant				ENSP00000513674
TLR3	ENST00000698352.1	c.*185+190G>C		intron_variant, NMD_transcript_variant				ENSP00000513675

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28192 AN: 151814 Hom.: 2798 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.186 AC: 28203 AN: 151932 Hom.: 2802 Cov.: 32 AF XY: 0.181 AC XY: 13440 AN XY: 74282

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0909 Hom.: 144

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.50

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: rs5743314; hg19: chr4-187000375;