dbSNP rs1773766: TLR5:c.-702G>T (chr1-223143343-C-A) – 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.-702G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 152,412 control chromosomes in the GnomAD database, including 815 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 0.080 ( 815 hom., cov: 33)

Exomes 𝑓: 0.016 ( 0 hom. )

Consequence

TLR5
NM_003268.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.658

Publications

6 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:

LOC124904522 (HGNC:):

LOC124904522 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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6 link	c.-702G>T		upstream_gene_variant		ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2 link	c.-702G>T		upstream_gene_variant			NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12073

AN:

152168

Hom.:

809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0939

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0578

GnomAD4 exome

AF:

0.0159

AC:

AN:

126

Hom.:

AF XY:

0.0204

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0200

AC:

AN:

100

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0795

AC:

12111

AN:

152286

Hom.:

815

Cov.:

AF XY:

0.0787

AC XY:

5862

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.179

AC:

7424

AN:

41544

American (AMR)

AF:

0.0387

AC:

593

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3472

East Asian (EAS)

AF:

0.0938

AC:

484

AN:

5162

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4830

European-Finnish (FIN)

AF:

0.0298

AC:

317

AN:

10626

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0409

AC:

2785

AN:

68020

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

542

1085

1627

2170

2712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0169

Hom.:

Bravo

AF:

0.0847

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

5.2

(source)

DANN

Benign

0.59

PhyloP100

0.66

PromoterAI

-0.041

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over