rs1773726

Variant names:

• chr1-223114572-G-A
• rs1773726
• NM_003268.6:c.-4-1537C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003268.6(TLR5):​c.-4-1537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,822 control chromosomes in the GnomAD database, including 9,947 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 0.34 (9947 hom., cov: 32)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-4-1537C>T		intron_variant	Intron 5 of 5	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-4-1537C>T		intron_variant	Intron 5 of 5		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51641 AN: 151700 Hom.: 9942 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51674 AN: 151822 Hom.: 9947 Cov.: 32 AF XY: 0.343 AC XY: 25428 AN XY: 74134

African (AFR) AF: 0.160 AC: 6635 AN: 41474

American (AMR) AF: 0.325 AC: 4969 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5152

South Asian (SAS) AF: 0.424 AC: 2038 AN: 4804

European-Finnish (FIN) AF: 0.491 AC: 5150 AN: 10492

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

European-Non Finnish (NFE) AF: 0.429 AC: 29137 AN: 67850

Other (OTH) AF: 0.343 AC: 724 AN: 2112

Alfa AF: 0.393 Hom.: 1534

Bravo AF: 0.316

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.34
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: rs1773726; hg19: chr1-223287914;