Variant 1-223110509-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003268.6(TLR5):c.2523A>G(p.Lys841=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,614,048 control chromosomes in the GnomAD database, including 7,323 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 0.069 ( 451 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6872 hom. )

Consequence

TLR5
NM_003268.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=0.457 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6 linkuse as main transcript	c.2523A>G	p.Lys841=	synonymous_variant	6/6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2 linkuse as main transcript	c.2523A>G	p.Lys841=	synonymous_variant	6/6		NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000540964.5 linkuse as main transcript	c.2523A>G	p.Lys841=	synonymous_variant	4/4	5		ENSP00000440643	P1

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

10500

AN:

152180

Hom.:

451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0724

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0321

Gnomad FIN

AF:

0.0717

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0927

GnomAD3 exomes

AF:

0.0744

AC:

18687

AN:

251192

Hom.:

911

AF XY:

0.0753

AC XY:

10228

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.0522

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0802

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0922

AC:

134743

AN:

1461750

Hom.:

6872

Cov.:

AF XY:

0.0914

AC XY:

66458

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.0543

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.0406

Gnomad4 FIN exome

AF:

0.0790

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0856

GnomAD4 genome

AF:

0.0689

AC:

10496

AN:

152298

Hom.:

451

Cov.:

AF XY:

0.0658

AC XY:

4900

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0189

Gnomad4 AMR

AF:

0.0722

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0325

Gnomad4 FIN

AF:

0.0717

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.0918

Alfa

AF:

0.0934

Hom.:

394

Bravo

AF:

0.0675

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.1

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over