rs5744190

Variant names:

• chr1-223109471-C-CA
• rs5744190
• NM_003268.6:c.*983dupT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus, susceptibility to, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ENSG00000299361 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003268.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	NM_003268.6	MANE Select	c.*983dupT		3_prime_UTR	Exon 6 of 6	NP_003259.2
	TLR5	NM_001437539.1		c.*983dupT		3_prime_UTR	Exon 6 of 6	NP_001424468.1	A0A2R8Y7Z4
	TLR5	NM_001437624.1		c.*983dupT		3_prime_UTR	Exon 4 of 4	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	ENST00000642603.2	MANE Select	c.*983dupT		3_prime_UTR	Exon 6 of 6	ENSP00000496355.1	A0A2R8Y7Z4
	TLR5	ENST00000407096.7	TSL:3	c.*983dupT		3_prime_UTR	Exon 4 of 4	ENSP00000385458.3	B1AZ06
	TLR5	ENST00000645434.2		c.*983dupT		3_prime_UTR	Exon 5 of 5	ENSP00000493892.2	O60602

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.119 AC: 4940 AN: 41486

American (AMR) AF: 0.321 AC: 4894 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1380 AN: 3462

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5168

South Asian (SAS) AF: 0.424 AC: 2040 AN: 4812

European-Finnish (FIN) AF: 0.489 AC: 5117 AN: 10460

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29141 AN: 67868

Other (OTH) AF: 0.334 AC: 706 AN: 2114

Alfa AF: 0.379 Hom.: 1254

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5744190; hg19: chr1-223282813;