dbSNP rs45506101: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6 link	c.-4-49T>C		intron_variant	Intron 5 of 5	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2 link	c.-4-49T>C		intron_variant	Intron 5 of 5		NM_003268.6	ENSP00000496355.1

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over