rs1861172

Positions:

• chr1-223109892-T-C

Variant summary

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

The NM_003268.6(TLR5):​c.*563A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 161,446 control chromosomes in the GnomAD database, including 12,186 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 0.38 (11500 hom., cov: 32)
  • Exomes 𝑓: 0.36 (686 hom.)
• Consequence: TLR5 NM_003268.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.*563A>G		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.*563A>G		3_prime_UTR_variant	6/6		NM_003268.6	ENSP00000496355.1
TLR5	ENST00000540964	c.*563A>G		3_prime_UTR_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57833 AN: 151898 Hom.: 11491 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.361 AC: 3403 AN: 9432 Hom.: 686 Cov.: 0 AF XY: 0.358 AC XY: 1829 AN XY: 5114

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.381 AC: 57889 AN: 152014 Hom.: 11500 Cov.: 32 AF XY: 0.382 AC XY: 28395 AN XY: 74302

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.365

Alfa AF: 0.402 Hom.: 3886

Bravo AF: 0.361

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.45

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: rs1861172; hg19: chr1-223283234;