rs45588337

Positions:

• chr4-38805707-A-G

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,134 control chromosomes in the GnomAD database, including 2,254 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 (2252 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2 hom.)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-514T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22265 AN: 151984 Hom.: 2252 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 2 AF XY: 0.333 AC XY: 8 AN XY: 24

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.227

GnomAD4 genome AF: 0.146 AC: 22258 AN: 152102 Hom.: 2252 Cov.: 32 AF XY: 0.145 AC XY: 10796 AN XY: 74338

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.202

Alfa AF: 0.152 Hom.: 288

Bravo AF: 0.152

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45588337; hg19: chr4-38807328;