rs4986791

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_138554(TLR4):c.1196C>T(p.Thr399Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152076 control chromosomes in the gnomAD Genomes database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.049 ( 250 hom., cov: 32)

Exomes 𝑓: 0.057 ( 537 hom. )

Consequence

TLR4
NM_138554 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.201

Links

TLR4 (HGNC:11850):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031039119).

BP6

Variant 9:117713324-C>T is Benign according to our data. Variant chr9-117713324-C-T is described in ClinVar as [Benign]. Clinvar id is 6661. Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-117713324-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR4	NM_138554.5 linkuse as main transcript	c.1196C>T	p.Thr399Ile	missense_variant	3/3	ENST00000355622.8
TLR4	NM_003266.4 linkuse as main transcript	c.1076C>T	p.Thr359Ile	missense_variant	4/4
TLR4	NM_138557.3 linkuse as main transcript	c.596C>T	p.Thr199Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR4	ENST00000355622.8 linkuse as main transcript	c.1196C>T	p.Thr399Ile	missense_variant	3/3	1	NM_138554.5	P1	O00206-1
TLR4	ENST00000394487.5 linkuse as main transcript	c.1076C>T	p.Thr359Ile	missense_variant	4/4	1			O00206-2
TLR4	ENST00000472304.2 linkuse as main transcript	c.*930C>T		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7511

AN:

152076

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0451

GnomAD3 exomes

AF:

0.0566

AC:

14176

AN:

250350

Hom.:

537

AF XY:

0.0602

AC XY:

8143

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.0266

Gnomad ASJ exome

AF:

0.0511

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0576

Gnomad OTH exome

AF:

0.0576

GnomAD4 exome

AF:

0.0625

AC:

91406

AN:

1461700

Hom.:

3347

AF XY:

0.0636

AC XY:

46272

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.0282

Gnomad4 ASJ exome

AF:

0.0519

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0626

Gnomad4 OTH exome

AF:

0.0648

Alfa

AF:

0.0562

Hom.:

550

Bravo

AF:

0.0409

TwinsUK

AF:

0.0510

AC:

189

ALSPAC

AF:

0.0563

AC:

217

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0626

AC:

538

ExAC

AF:

0.0550

AC:

6681

Asia WGS

AF:

0.0640

AC:

221

AN:

3474

EpiCase

AF:

0.0612

EpiControl

AF:

0.0576

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR4 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 18, 2002

- -

not provided

Other:1

not provided, no assertion provided

literature only

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.60

Cadd

Benign

2.6

Dann

Uncertain

0.97

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.51

T;.;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

9.8e-12

A;A

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

N;.;N

REVEL

Benign

0.016

Sift

Uncertain

0.024

D;.;D

Sift4G

Benign

0.090

T;.;T

Polyphen

0.18

.;B;B

Vest4

0.063

MPC

0.12

ClinPred

0.0079

GERP RS

0.43

Varity_R

0.21

gMVP

0.40

Splicing

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over