rs1773727

Variant names:

• chr1-223113209-A-C
• rs1773727
• NM_003268.6:c.-4-174T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-223113209-A-C
• chr1-223113209-A-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.-4-174T>G 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 151,604 control chromosomes in the GnomAD database, including 9,952 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 (9952 hom., cov: 32)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	NM_003268.6	MANE Select	c.-4-174T>G		intron	N/A	NP_003259.2
	TLR5	NM_001437539.1		c.-4-174T>G		intron	N/A	NP_001424468.1
	TLR5	NM_001437624.1		c.-4-174T>G		intron	N/A	NP_001424553.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	ENST00000642603.2	MANE Select	c.-4-174T>G		intron	N/A	ENSP00000496355.1
	TLR5	ENST00000407096.7	TSL:3	c.-4-174T>G		intron	N/A	ENSP00000385458.3
	TLR5	ENST00000484766.2	TSL:3	c.-4-174T>G		intron	N/A	ENSP00000519510.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51531 AN: 151484 Hom.: 9948 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.340 AC: 51564 AN: 151604 Hom.: 9952 Cov.: 32 AF XY: 0.343 AC XY: 25380 AN XY: 74082

African (AFR) AF: 0.157 AC: 6466 AN: 41306

American (AMR) AF: 0.326 AC: 4972 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3460

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5146

South Asian (SAS) AF: 0.425 AC: 2042 AN: 4806

European-Finnish (FIN) AF: 0.493 AC: 5167 AN: 10478

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

European-Non Finnish (NFE) AF: 0.430 AC: 29172 AN: 67832

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.392 Hom.: 1565

Bravo AF: 0.315

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-2.0
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: rs1773727; hg19: chr1-223286551;