dbSNP rs851181: TLR5:c.-169-125C>T (chr1-223132764-G-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.-169-125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,094 control chromosomes in the GnomAD database, including 33,372 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 0.65 ( 33372 hom., cov: 33)

Exomes 𝑓: 0.51 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

TLR5
NM_003268.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

Publications

3 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 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.-169-125C>T	intron	N/A	NP_003259.2
TLR5	NM_001437539.1		c.-169-125C>T	intron	N/A	NP_001424468.1	A0A2R8Y7Z4
TLR5	NM_001437624.1		c.-169-125C>T	intron	N/A	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR5	ENST00000642603.2	MANE Select	c.-169-125C>T	intron	N/A	ENSP00000496355.1	A0A2R8Y7Z4
TLR5	ENST00000964752.1		c.-294C>T	5_prime_UTR	Exon 3 of 4	ENSP00000634811.1
TLR5	ENST00000407096.7	TSL:3	c.-169-125C>T	intron	N/A	ENSP00000385458.3	B1AZ06

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99072

AN:

151976

Hom.:

33338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.661

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.512

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.652

AC:

99159

AN:

152094

Hom.:

33372

Cov.:

AF XY:

0.650

AC XY:

48287

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.816

AC:

33890

AN:

41518

American (AMR)

AF:

0.671

AC:

10238

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2073

AN:

3470

East Asian (EAS)

AF:

0.795

AC:

4117

AN:

5180

South Asian (SAS)

AF:

0.572

AC:

2758

AN:

4818

European-Finnish (FIN)

AF:

0.507

AC:

5354

AN:

10556

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38707

AN:

67970

Other (OTH)

AF:

0.658

AC:

1388

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1722

3444

5167

6889

8611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.602

Hom.:

3524

Bravo

AF:

0.675

Asia WGS

AF:

0.698

AC:

2427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.43

(source)

DANN

Benign

0.49

PhyloP100

-0.40

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over