Variant chr9-117712617-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_138554.5(TLR4):c.489A>G(p.Gln163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,613,998 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

TLR4
NM_138554.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.223

Variant links:

Genes affected

TLR4 (HGNC:11850): (toll like receptor 4) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

TLR4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-117712617-A-G is Benign according to our data. Variant chr9-117712617-A-G is described in ClinVar as [Benign]. Clinvar id is 717914.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.223 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR4	NM_138554.5 linkuse as main transcript	c.489A>G	p.Gln163=	synonymous_variant	3/3	ENST00000355622.8
TLR4	NM_003266.4 linkuse as main transcript	c.369A>G	p.Gln123=	synonymous_variant	4/4
TLR4	NM_138557.3 linkuse as main transcript	c.-112A>G		5_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR4	ENST00000355622.8 linkuse as main transcript	c.489A>G	p.Gln163=	synonymous_variant	3/3	1	NM_138554.5	P1	O00206-1
TLR4	ENST00000394487.5 linkuse as main transcript	c.369A>G	p.Gln123=	synonymous_variant	4/4	1			O00206-2
TLR4	ENST00000472304.2 linkuse as main transcript	c.*223A>G		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

449

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00995

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000662

AC:

166

AN:

250638

Hom.:

AF XY:

0.000502

AC XY:

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.00862

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000315

AC:

460

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

207

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00965

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00296

AC:

450

AN:

152222

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00336

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

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

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.60

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