Variant chr1-223110778-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003268.6(TLR5):c.2254A>G(p.Arg752Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 1,614,264 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

TLR5
NM_003268.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0147899985).

BP6

Variant 1-223110778-T-C is Benign according to our data. Variant chr1-223110778-T-C is described in ClinVar as [Benign]. Clinvar id is 791835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6 linkuse as main transcript	c.2254A>G	p.Arg752Gly	missense_variant	6/6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TLR5	ENST00000642603.2 linkuse as main transcript	c.2254A>G	p.Arg752Gly	missense_variant	6/6		NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000540964.5 linkuse as main transcript	c.2254A>G	p.Arg752Gly	missense_variant	4/4	5		ENSP00000440643	P1
TLR5	ENST00000645434.1 linkuse as main transcript	c.2254A>G	p.Arg752Gly	missense_variant	5/5			ENSP00000493892

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00931

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000712

AC:

179

AN:

251366

Hom.:

AF XY:

0.000537

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000252

AC:

368

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

144

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.00268

AC:

409

AN:

152380

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00928

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000486

Hom.:

Bravo

AF:

0.00295

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000964

AC:

117

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;.;.;D

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.74

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.1

D;.;D;.

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;.;D;.

Sift4G

Uncertain

0.0040

D;.;D;.

Vest4

0.76

MVP

0.59

MPC

0.39

ClinPred

0.081

GERP RS

2.1

gMVP

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over