Variant rs5744169 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003268.6(TLR5):c.1332C>T(p.Leu444Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,614,154 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 84 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 82 hom. )

Consequence

TLR5
NM_003268.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0550

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:

TLR5 (HGNC:):

TLR5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-223111700-G-A is Benign according to our data. Variant chr1-223111700-G-A is described in ClinVar as [Benign]. Clinvar id is 775671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.055 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 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.1332C>T	p.Leu444Leu	synonymous_variant	6/6	ENST00000642603.2	NP_003259.2	O60602A0A2R8Y7Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TLR5	ENST00000642603.2 linkuse as main transcript	c.1332C>T	p.Leu444Leu	synonymous_variant	6/6		NM_003268.6	ENSP00000496355.1	A0A2R8Y7Z4
TLR5	ENST00000540964.5 linkuse as main transcript	c.1332C>T	p.Leu444Leu	synonymous_variant	4/4	5			O60602
TLR5	ENST00000645434.1 linkuse as main transcript	c.1332C>T	p.Leu444Leu	synonymous_variant	5/5			ENSP00000493892.2	A0A2R8Y4Q2

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2919

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00509

AC:

1280

AN:

251252

Hom.:

AF XY:

0.00370

AC XY:

502

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0689

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00199

AC:

2916

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1274

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0663

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.0193

AC:

2933

AN:

152288

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1388

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.51

DANN

Benign

0.53

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