dbSNP rs3044336: TLR5:c.-246_-245insTGAGTAGC (chr1-223134757-T-TGCTACTCA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003268.6(TLR5):c.-246_-245insTGAGTAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,298 control chromosomes in the GnomAD database, including 784 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.073 ( 784 hom., cov: 31)

Exomes 𝑓: 0.035 ( 0 hom. )

Consequence

TLR5
NM_003268.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

1 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.-246_-245insTGAGTAGC	5_prime_UTR	Exon 4 of 6	NP_003259.2
TLR5	NM_001437539.1		c.-340_-339insTGAGTAGC	5_prime_UTR	Exon 3 of 6	NP_001424468.1	A0A2R8Y7Z4
TLR5	NM_001437624.1		c.-246_-245insTGAGTAGC	5_prime_UTR	Exon 2 of 4	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR5	ENST00000642603.2	MANE Select	c.-246_-245insTGAGTAGC	5_prime_UTR	Exon 4 of 6	ENSP00000496355.1	A0A2R8Y7Z4
TLR5	ENST00000407096.7	TSL:3	c.-246_-245insTGAGTAGC	5_prime_UTR	Exon 2 of 4	ENSP00000385458.3	B1AZ06
TLR5	ENST00000484766.2	TSL:3	c.-340_-339insTGAGTAGC	5_prime_UTR	Exon 4 of 7	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11134

AN:

152036

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0911

Gnomad SAS

AF:

0.0471

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0308

Gnomad OTH

AF:

0.0516

GnomAD4 exome

AF:

0.0347

AC:

AN:

144

Hom.:

Cov.:

AF XY:

0.0513

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0368

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0734

AC:

11172

AN:

152154

Hom.:

784

Cov.:

AF XY:

0.0725

AC XY:

5392

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.181

AC:

7498

AN:

41446

American (AMR)

AF:

0.0327

AC:

500

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.0909

AC:

470

AN:

5170

South Asian (SAS)

AF:

0.0471

AC:

227

AN:

4820

European-Finnish (FIN)

AF:

0.0193

AC:

205

AN:

10616

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0308

AC:

2097

AN:

68022

Other (OTH)

AF:

0.0510

AC:

108

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

468

936

1403

1871

2339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0555

Hom.:

Bravo

AF:

0.0788

Asia WGS

AF:

0.0650

AC:

224

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=300/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over