rs45506101

Positions:

• chr1-223113084-A-G

Variant summary

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

The NM_003268.6(TLR5):​c.-4-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,575,922 control chromosomes in the GnomAD database, including 241 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 0.0046 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (221 hom.)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-4-49T>C		intron_variant		ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-4-49T>C		intron_variant			NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000407096.6	c.-4-49T>C		intron_variant		3		ENSP00000385458
TLR5	ENST00000540964.5	c.-4-49T>C		intron_variant		5		ENSP00000440643	P1
TLR5	ENST00000645434.1	c.-4-49T>C		intron_variant				ENSP00000493892

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 705 AN: 152162 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00487 AC: 6932 AN: 1423642 Hom.: 221 Cov.: 26 AF XY: 0.00626 AC XY: 4446 AN XY: 710400

Gnomad4 AFR exome AF: 0.000519

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0518

Gnomad4 SAS exome AF: 0.0509

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000334

Gnomad4 OTH exome AF: 0.00826

GnomAD4 genome AF: 0.00465 AC: 708 AN: 152280 Hom.: 20 Cov.: 32 AF XY: 0.00573 AC XY: 427 AN XY: 74476

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.0606

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00309

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs45506101; hg19: chr1-223286426;