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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

2
14

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.201

Links

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 UniProt
TLR4NM_138554.5 linkuse as main transcriptc.1196C>T p.Thr399Ile missense_variant 3/3 ENST00000355622.8
TLR4NM_003266.4 linkuse as main transcriptc.1076C>T p.Thr359Ile missense_variant 4/4
TLR4NM_138557.3 linkuse as main transcriptc.596C>T p.Thr199Ile missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR4ENST00000355622.8 linkuse as main transcriptc.1196C>T p.Thr399Ile missense_variant 3/31 NM_138554.5 P1O00206-1
TLR4ENST00000394487.5 linkuse as main transcriptc.1076C>T p.Thr359Ile missense_variant 4/41 O00206-2
TLR4ENST00000472304.2 linkuse as main transcriptc.*930C>T 3_prime_UTR_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.0494
AC:
7511
AN:
152076
Hom.:
250
Cov.:
32
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:
73
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 providedliterature onlyOMIMJul 18, 2002- -
not provided Other:1
not provided, no assertion providedliterature onlyNEI 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
T
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
N
LIST_S2
Benign
0.51
T;.;T
MetaRNN
Benign
0.0031
T;T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
9.8e-12
A;A
PrimateAI
Benign
0.37
T
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
T
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.

Other links and lift over

dbSNP: rs4986791; hg19: chr9-120475602; COSMIC: COSV62922311; COSMIC: COSV62922311;