Genetic Variant TLR5:c.-4-2970A>G (chr1-223116005-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.-4-2970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,110 control chromosomes in the GnomAD database, including 36,836 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 0.68 ( 36836 hom., cov: 32)

Consequence

TLR5
NM_003268.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.55

Publications

7 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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus, susceptibility to, 1
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 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	UniProt
TLR5	NM_003268.6	MANE Select	c.-4-2970A>G	intron	N/A	NP_003259.2
TLR5	NM_001437539.1		c.-4-2970A>G	intron	N/A	NP_001424468.1	A0A2R8Y7Z4
TLR5	NM_001437624.1		c.-4-2970A>G	intron	N/A	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR5	ENST00000642603.2	MANE Select	c.-4-2970A>G	intron	N/A	ENSP00000496355.1	A0A2R8Y7Z4
TLR5	ENST00000407096.7	TSL:3	c.-4-2970A>G	intron	N/A	ENSP00000385458.3	B1AZ06
TLR5	ENST00000484766.2	TSL:3	c.-4-2970A>G	intron	N/A	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

104032

AN:

151992

Hom.:

36807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.791

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.684

AC:

104115

AN:

152110

Hom.:

36836

Cov.:

AF XY:

0.680

AC XY:

50528

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.871

AC:

36170

AN:

41532

American (AMR)

AF:

0.691

AC:

10553

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2123

AN:

3470

East Asian (EAS)

AF:

0.791

AC:

4088

AN:

5168

South Asian (SAS)

AF:

0.587

AC:

2824

AN:

4810

European-Finnish (FIN)

AF:

0.526

AC:

5555

AN:

10556

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.600

AC:

40761

AN:

67980

Other (OTH)

AF:

0.666

AC:

1404

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.577

Hom.:

7528

Bravo

AF:

0.708

Asia WGS

AF:

0.708

AC:

2463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.41

(source)

DANN

Benign

0.27

PhyloP100

-3.5

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over