rs5743595

Positions:

• chr4-38801023-A-G

Variant summary

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

The NM_003263.4(TLR1):​c.-159-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,644 control chromosomes in the GnomAD database, including 2,214 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 (2210 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4 hom.)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4	c.-159-75T>C		intron_variant		ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000308979.7	c.-159-75T>C		intron_variant		1	NM_003263.4	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22116 AN: 152084 Hom.: 2210 Cov.: 32

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.100 AC: 44 AN: 440 Hom.: 4 AF XY: 0.124 AC XY: 33 AN XY: 266

Gnomad4 FIN exome AF: 0.0981

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.145 AC: 22109 AN: 152204 Hom.: 2210 Cov.: 32 AF XY: 0.144 AC XY: 10713 AN XY: 74406

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.199

Alfa AF: 0.153 Hom.: 355

Bravo AF: 0.151

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.86

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: rs5743595; hg19: chr4-38802644;