chr1-223109471-C-CA

Position:

• chr1-223109471-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003268.6(TLR5):​c.*983dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9679 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: TLR5 NM_003268.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

Genes affected

TLR5 (HGNC:11851): (toll like receptor 5) This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]

TLR5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.*983dupT		3_prime_UTR_variant	6/6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603	c.*983dupT		3_prime_UTR_variant	6/6		NM_003268.6	ENSP00000496355.1
TLR5	ENST00000540964	c.*983dupT		3_prime_UTR_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49833 AN: 151706 Hom.: 9674 Cov.: 0

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.328 AC: 49861 AN: 151824 Hom.: 9679 Cov.: 0 AF XY: 0.331 AC XY: 24552 AN XY: 74138

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.334

Alfa AF: 0.379 Hom.: 1254

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs5744190; hg19: chr1-223282813;