Genetic Variant TLR5:c.-4-49T>C (chr1-223113084-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003268.6(TLR5):c.-4-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,575,922 control chromosomes in the GnomAD database, including 241 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 0.0046 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 221 hom. )

Consequence

TLR5
NM_003268.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.695

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.06 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TLR5	NM_003268.6	MANE Select	c.-4-49T>C	intron	N/A	NP_003259.2
TLR5	NM_001437539.1		c.-4-49T>C	intron	N/A	NP_001424468.1
TLR5	NM_001437624.1		c.-4-49T>C	intron	N/A	NP_001424553.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TLR5	ENST00000642603.2	MANE Select	c.-4-49T>C	intron	N/A	ENSP00000496355.1
TLR5	ENST00000407096.7	TSL:3	c.-4-49T>C	intron	N/A	ENSP00000385458.3
TLR5	ENST00000484766.2	TSL:3	c.-4-49T>C	intron	N/A	ENSP00000519510.1

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

705

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.0599

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00487

AC:

6932

AN:

1423642

Hom.:

221

Cov.:

AF XY:

0.00626

AC XY:

4446

AN XY:

710400

show subpopulations

African (AFR)

AF:

0.000519

AC:

AN:

32738

American (AMR)

AF:

0.000249

AC:

AN:

44172

Ashkenazi Jewish (ASJ)

AF:

0.0000388

AC:

AN:

25794

East Asian (EAS)

AF:

0.0518

AC:

2046

AN:

39470

South Asian (SAS)

AF:

0.0509

AC:

4323

AN:

84936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52834

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1078836

Other (OTH)

AF:

0.00826

AC:

489

AN:

59170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

406

813

1219

1626

2032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00465

AC:

708

AN:

152280

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

427

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41562

American (AMR)

AF:

0.00144

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0658

AC:

341

AN:

5184

South Asian (SAS)

AF:

0.0606

AC:

292

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68004

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00309

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.73

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over