rs5743558

Variant names:

• chr4-38804814-A-AAG
• rs5743558
• ENST00000505744.6:n.5_6insCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000505744.6(TLR1):​n.5_6insCT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,236 control chromosomes in the GnomAD database, including 2,231 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2231 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: TLR1 ENST00000505744.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 1 publications found

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]

ENSG00000306984 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• 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 rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-298_-297insCT		upstream_gene_variant		ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-298_-297insCT		upstream_gene_variant		1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22230 AN: 152118 Hom.: 2231 Cov.: 30

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.205

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22223 AN: 152236 Hom.: 2231 Cov.: 30 AF XY: 0.145 AC XY: 10776 AN XY: 74422

African (AFR) AF: 0.0343 AC: 1426 AN: 41564

American (AMR) AF: 0.174 AC: 2668 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2078 AN: 5168

South Asian (SAS) AF: 0.196 AC: 945 AN: 4824

European-Finnish (FIN) AF: 0.0838 AC: 889 AN: 10614

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12376 AN: 67982

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.148 Hom.: 230

Bravo AF: 0.152

Asia WGS AF: 0.235 AC: 816 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5743558; hg19: chr4-38806435;