rs3044336

Variant names:

• chr1-223134757-T-TGCTACTCA
• rs3044336
• NM_003268.6:c.-246_-245insTGAGTAGC

Variant summary

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

The NM_003268.6(TLR5):​c.-246_-245insTGAGTAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,298 control chromosomes in the GnomAD database, including 784 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (784 hom., cov: 31)
  • Exomes 𝑓: 0.035 (0 hom.)
• Consequence: TLR5 NM_003268.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 1 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]

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-246_-245insTGAGTAGC		5_prime_UTR_variant	Exon 4 of 6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-246_-245insTGAGTAGC		5_prime_UTR_variant	Exon 4 of 6		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11134 AN: 152036 Hom.: 778 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0347 AC: 5 AN: 144 Hom.: 0 Cov.: 0 AF XY: 0.0513 AC XY: 4 AN XY: 78

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0368 AC: 5 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0734 AC: 11172 AN: 152154 Hom.: 784 Cov.: 31 AF XY: 0.0725 AC XY: 5392 AN XY: 74402

African (AFR) AF: 0.181 AC: 7498 AN: 41446

American (AMR) AF: 0.0327 AC: 500 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.0909 AC: 470 AN: 5170

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4820

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10616

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0308 AC: 2097 AN: 68022

Other (OTH) AF: 0.0510 AC: 108 AN: 2116

Alfa AF: 0.0555 Hom.: 53

Bravo AF: 0.0788

Asia WGS AF: 0.0650 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3044336; hg19: chr1-223308099; COSMIC: COSV60560064; COSMIC: COSV60560064;