Variant rs5744168 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003268.6(TLR5):c.1174C>T(p.Arg392Ter) 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

Scores

Clinical Significance

protective; risk factor no assertion criteria provided B:2O:1

Conservation

PhyloP100: 1.96

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6 linkuse as main transcript	c.1174C>T	p.Arg392Ter	stop_gained	6/6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TLR5	ENST00000642603.2 linkuse as main transcript	c.1174C>T	p.Arg392Ter	stop_gained	6/6		NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000540964.5 linkuse as main transcript	c.1174C>T	p.Arg392Ter	stop_gained	4/4	5		ENSP00000440643	P1
TLR5	ENST00000645434.1 linkuse as main transcript	c.1174C>T	p.Arg392Ter	stop_gained	5/5			ENSP00000493892

Frequencies

GnomAD3 genomes

AF:

0.0442

AC:

6732

AN:

152144

Hom.:

187

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0530

AC:

13309

AN:

251130

Hom.:

458

AF XY:

0.0569

AC XY:

7732

AN XY:

135796

show subpopulations

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 SAS exome

AF:

0.103

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.:

AF XY:

0.0619

AC XY:

44987

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.0217

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.0177

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0515

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.0545

GnomAD4 genome

AF:

0.0442

AC:

6728

AN:

152262

Hom.:

188

Cov.:

AF XY:

0.0444

AC XY:

3308

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.0272

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0443

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0551

Hom.:

431

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

Significance: protective; risk factor

Submissions summary: Benign:2Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Systemic lupus erythematosus, resistance to, 1

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Apr 01, 2013

- -

Melioidosis, resistance to

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Apr 01, 2013

- -

Legionnaire disease, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

MutationTaster

Benign

1.0

D;D;D

Vest4

0.94

GERP RS

4.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over