Genetic Variant NM_003268.6:c.*563A>G (chr1-223109892-T-C) – 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.*563A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 161,446 control chromosomes in the GnomAD database, including 12,186 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 0.38 ( 11500 hom., cov: 32)

Exomes 𝑓: 0.36 ( 686 hom. )

Consequence

TLR5
NM_003268.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.662

Publications

4 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:

ENSG00000299361 (HGNC:):

ENSG00000299361 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6 link	c.*563A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2 link	c.*563A>G		3_prime_UTR_variant	Exon 6 of 6		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57833

AN:

151898

Hom.:

11491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.361

AC:

3403

AN:

9432

Hom.:

686

Cov.:

AF XY:

0.358

AC XY:

1829

AN XY:

5114

show subpopulations

African (AFR)

AF:

0.184

AC:

AN:

American (AMR)

AF:

0.278

AC:

490

AN:

1762

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

AN:

East Asian (EAS)

AF:

0.216

AC:

111

AN:

514

South Asian (SAS)

AF:

0.371

AC:

367

AN:

988

European-Finnish (FIN)

AF:

0.453

AC:

AN:

150

Middle Eastern (MID)

AF:

0.357

AC:

AN:

European-Non Finnish (NFE)

AF:

0.398

AC:

2204

AN:

5542

Other (OTH)

AF:

0.371

AC:

127

AN:

342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

182

274

365

456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.381

AC:

57889

AN:

152014

Hom.:

11500

Cov.:

AF XY:

0.382

AC XY:

28395

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.298

AC:

12348

AN:

41434

American (AMR)

AF:

0.339

AC:

5176

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1393

AN:

3468

East Asian (EAS)

AF:

0.209

AC:

1079

AN:

5164

South Asian (SAS)

AF:

0.425

AC:

2049

AN:

4822

European-Finnish (FIN)

AF:

0.494

AC:

5214

AN:

10564

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.431

AC:

29291

AN:

67976

Other (OTH)

AF:

0.365

AC:

771

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1852

3704

5557

7409

9261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.404

Hom.:

6667

Bravo

AF:

0.361

Asia WGS

AF:

0.312

AC:

1086

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.6

(source)

DANN

Benign

0.45

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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