rs5743592

chr4-38801442-A-Gchr4-38801442-A-T

Variant summary

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

The NM_003263.4(TLR1):c.-159-494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,274 control chromosomes in the GnomAD database, including 2,264 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 0.15 (2264 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) 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 gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4	c.-159-494T>C		intron_variant		ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000308979.7	c.-159-494T>C		intron_variant		1	NM_003263.4	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22316 AN: 152156 Hom.: 2263 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.147 AC: 22309 AN: 152274 Hom.: 2264 Cov.: 32 AF XY: 0.145 AC XY: 10823 AN XY: 74446

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.202

Alfa AF: 0.152 Hom.: 423

Bravo AF: 0.152

Asia WGS AF: 0.243 AC: 845 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	0.58
Dann	Benign	0.43

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: rs5743592; hg19: chr4-38803063;