dbSNP rs851183: TLR5:c.-5+36C>G (chr1-223132439-G-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.-5+36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,602 control chromosomes in the GnomAD database, including 33,152 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 ( 33152 hom., cov: 32)

Exomes 𝑓: 0.54 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

TLR5
NM_003268.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.00

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:

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=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6 link	c.-5+36C>G		intron_variant	Intron 5 of 5	ENST00000642603.2	NP_003259.2	O60602A0A2R8Y7Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2 link	c.-5+36C>G		intron_variant	Intron 5 of 5		NM_003268.6	ENSP00000496355.1		A0A2R8Y7Z4

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98626

AN:

151482

Hom.:

33116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.494

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.657

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.536

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.539

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.536

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.386

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:

0.651

AC:

98718

AN:

151602

Hom.:

33152

Cov.:

AF XY:

0.649

AC XY:

48053

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.816

AC:

33721

AN:

41338

American (AMR)

AF:

0.670

AC:

10214

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2067

AN:

3464

East Asian (EAS)

AF:

0.793

AC:

4076

AN:

5140

South Asian (SAS)

AF:

0.573

AC:

2753

AN:

4808

European-Finnish (FIN)

AF:

0.505

AC:

5297

AN:

10494

Middle Eastern (MID)

AF:

0.621

AC:

180

AN:

290

European-Non Finnish (NFE)

AF:

0.569

AC:

38581

AN:

67816

Other (OTH)

AF:

0.656

AC:

1380

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1693

3386

5080

6773

8466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.592

Hom.:

3228

Bravo

AF:

0.675

Asia WGS

AF:

0.699

AC:

2429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.72

(source)

DANN

Benign

0.44

PhyloP100

-4.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over