Genetic Variant TLR5:c.-438-1002G>A (chr1-223138265-C-T) – 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.-438-1002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,642 control chromosomes in the GnomAD database, including 35,328 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 0.66 ( 35328 hom., cov: 30)

Consequence

TLR5
NM_003268.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

11 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:

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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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 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.-438-1002G>A	intron	N/A	NP_003259.2
TLR5	NM_001437539.1		c.-532-1002G>A	intron	N/A	NP_001424468.1	A0A2R8Y7Z4
TLR5	NM_001437624.1		c.-352-3401G>A	intron	N/A	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR5	ENST00000642603.2	MANE Select	c.-438-1002G>A	intron	N/A	ENSP00000496355.1	A0A2R8Y7Z4
TLR5	ENST00000407096.7	TSL:3	c.-352-3401G>A	intron	N/A	ENSP00000385458.3	B1AZ06
TLR5	ENST00000484766.2	TSL:3	c.-532-1002G>A	intron	N/A	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

100628

AN:

151522

Hom.:

35279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.645

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

GnomAD4 genome

AF:

0.664

AC:

100727

AN:

151642

Hom.:

35328

Cov.:

AF XY:

0.662

AC XY:

49056

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.885

AC:

36640

AN:

41380

American (AMR)

AF:

0.661

AC:

10078

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2021

AN:

3466

East Asian (EAS)

AF:

0.851

AC:

4390

AN:

5156

South Asian (SAS)

AF:

0.627

AC:

3012

AN:

4802

European-Finnish (FIN)

AF:

0.496

AC:

5185

AN:

10464

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37445

AN:

67808

Other (OTH)

AF:

0.644

AC:

1354

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1482

2964

4447

5929

7411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.593

Hom.:

33517

Bravo

AF:

0.689

Asia WGS

AF:

0.745

AC:

2590

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.18

(source)

DANN

Benign

0.49

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over