rs5744168

Variant names:

• chr1-223111858-G-A
• rs5744168
• NM_003268.6:c.1174C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-223111858-G-A
• chr1-223111858-G-C
• chr1-223111858-G-T

Variant summary

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

The NM_003268.6(TLR5):​c.1174C>T​(p.Arg392*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 1,613,796 control chromosomes in the GnomAD database, including 3,257 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as protective,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.044 (188 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3069 hom.)
• Consequence: TLR5 NM_003268.6 stop_gained
• Clinical Significance: protective; risk factor no assertion criteria provided B:2 O:1
• Conservation: PhyloP100: 1.96
• Publications: 181 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 (SAS) allele frequency at 95% confidence interval = 0.0943 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.1174C>T	p.Arg392*	stop_gained	Exon 6 of 6	NP_003259.2
	TLR5	NM_001437539.1		c.1174C>T	p.Arg392*	stop_gained	Exon 6 of 6	NP_001424468.1	A0A2R8Y7Z4
	TLR5	NM_001437624.1		c.1174C>T	p.Arg392*	stop_gained	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.1174C>T	p.Arg392*	stop_gained	Exon 6 of 6	ENSP00000496355.1	A0A2R8Y7Z4
	TLR5	ENST00000407096.7	TSL:3	c.1174C>T	p.Arg392*	stop_gained	Exon 4 of 4	ENSP00000385458.3	B1AZ06
	TLR5	ENST00000484766.2	TSL:3	c.1174C>T	p.Arg392*	stop_gained	Exon 7 of 7	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6732 AN: 152144 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0443

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0420

GnomAD2 exomes AF: 0.0530 AC: 13309 AN: 251130 AF XY: 0.0569

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.0195

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.0279

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0618

Gnomad OTH exome AF: 0.0491

GnomAD4 exome AF: 0.0607 AC: 88669 AN: 1461534 Hom.: 3069 Cov.: 36 AF XY: 0.0619 AC XY: 44987 AN XY: 727034

African (AFR) AF: 0.0217 AC: 726 AN: 33456

American (AMR) AF: 0.0200 AC: 896 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0287 AC: 750 AN: 26132

East Asian (EAS) AF: 0.0177 AC: 702 AN: 39684

South Asian (SAS) AF: 0.101 AC: 8684 AN: 86234

European-Finnish (FIN) AF: 0.0515 AC: 2749 AN: 53336

Middle Eastern (MID) AF: 0.0572 AC: 330 AN: 5766

European-Non Finnish (NFE) AF: 0.0634 AC: 70539 AN: 1111830

Other (OTH) AF: 0.0545 AC: 3293 AN: 60388

GnomAD4 genome AF: 0.0442 AC: 6728 AN: 152262 Hom.: 188 Cov.: 32 AF XY: 0.0444 AC XY: 3308 AN XY: 74454

African (AFR) AF: 0.0237 AC: 985 AN: 41556

American (AMR) AF: 0.0303 AC: 464 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3470

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5176

South Asian (SAS) AF: 0.102 AC: 490 AN: 4814

European-Finnish (FIN) AF: 0.0443 AC: 470 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3945 AN: 68022

Other (OTH) AF: 0.0430 AC: 91 AN: 2116

Alfa AF: 0.0545 Hom.: 921

Bravo AF: 0.0400

TwinsUK AF: 0.0588 AC: 218

ALSPAC AF: 0.0649 AC: 250

ESP6500AA AF: 0.0241 AC: 106

ESP6500EA AF: 0.0547 AC: 470

ExAC AF: 0.0556 AC: 6747

Asia WGS AF: 0.0890 AC: 312 AN: 3478

EpiCase AF: 0.0574

EpiControl AF: 0.0559

ClinVar

ClinVar submissions

Significance: protective; risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Legionnaire disease, susceptibility to (1)
-	-	-	Melioidosis, resistance to (1)
-	-	-	Systemic lupus erythematosus, resistance to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		2.0
Vest4		0.94
GERP RS		4.7
Mutation Taster		=179/21	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: rs5744168; hg19: chr1-223285200; COSMIC: COSV60558477; COSMIC: COSV60558477;