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rs4833095

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003263.4(TLR1):c.743A>G(p.Asn248Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,238 control chromosomes in the GnomAD database, including 90,036 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 (★).

Frequency

Genomes: 𝑓 0.44 ( 19255 hom., cov: 32)
Exomes 𝑓: 0.27 ( 70781 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

1
17

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.964
Variant links:
Genes affected
TLR1 (HGNC:11847): (toll like receptor 1) 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 (PAMPs) 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. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.6334178E-6).
BP6
Variant 4-38798089-T-C is Benign according to our data. Variant chr4-38798089-T-C is described in ClinVar as [Benign]. Clinvar id is 8361.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR1NM_003263.4 linkuse as main transcriptc.743A>G p.Asn248Ser missense_variant 4/4 ENST00000308979.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR1ENST00000308979.7 linkuse as main transcriptc.743A>G p.Asn248Ser missense_variant 4/41 NM_003263.4 P1
TLR1ENST00000502213.6 linkuse as main transcriptc.743A>G p.Asn248Ser missense_variant 3/31 P1
TLR1ENST00000505744.5 linkuse as main transcriptn.235+2768A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.436
AC:
66260
AN:
152006
Hom.:
19203
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.791
Gnomad AMI
AF:
0.318
Gnomad AMR
AF:
0.503
Gnomad ASJ
AF:
0.418
Gnomad EAS
AF:
0.597
Gnomad SAS
AF:
0.490
Gnomad FIN
AF:
0.114
Gnomad MID
AF:
0.566
Gnomad NFE
AF:
0.239
Gnomad OTH
AF:
0.483
GnomAD3 exomes
AF:
0.381
AC:
95308
AN:
250080
Hom.:
22422
AF XY:
0.374
AC XY:
50670
AN XY:
135426
show subpopulations
Gnomad AFR exome
AF:
0.801
Gnomad AMR exome
AF:
0.517
Gnomad ASJ exome
AF:
0.414
Gnomad EAS exome
AF:
0.595
Gnomad SAS exome
AF:
0.486
Gnomad FIN exome
AF:
0.120
Gnomad NFE exome
AF:
0.266
Gnomad OTH exome
AF:
0.368
GnomAD4 exome
AF:
0.273
AC:
399521
AN:
1461114
Hom.:
70781
Cov.:
36
AF XY:
0.279
AC XY:
202717
AN XY:
726712
show subpopulations
Gnomad4 AFR exome
AF:
0.808
Gnomad4 AMR exome
AF:
0.513
Gnomad4 ASJ exome
AF:
0.412
Gnomad4 EAS exome
AF:
0.634
Gnomad4 SAS exome
AF:
0.481
Gnomad4 FIN exome
AF:
0.124
Gnomad4 NFE exome
AF:
0.218
Gnomad4 OTH exome
AF:
0.329
GnomAD4 genome
AF:
0.436
AC:
66372
AN:
152124
Hom.:
19255
Cov.:
32
AF XY:
0.435
AC XY:
32398
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.791
Gnomad4 AMR
AF:
0.503
Gnomad4 ASJ
AF:
0.418
Gnomad4 EAS
AF:
0.597
Gnomad4 SAS
AF:
0.490
Gnomad4 FIN
AF:
0.114
Gnomad4 NFE
AF:
0.239
Gnomad4 OTH
AF:
0.486
Alfa
AF:
0.316
Hom.:
16136
Bravo
AF:
0.480
TwinsUK
AF:
0.226
AC:
837
ALSPAC
AF:
0.248
AC:
954
ESP6500AA
AF:
0.777
AC:
3424
ESP6500EA
AF:
0.249
AC:
2141
ExAC
AF:
0.393
AC:
47671
Asia WGS
AF:
0.564
AC:
1960
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TLR1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Leprosy, susceptibility to, 5 Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJun 15, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.80
T
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.27
Dann
Benign
0.43
DEOGEN2
Benign
0.24
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.060
T;.
MetaRNN
Benign
0.0000026
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.028
Sift
Benign
0.17
T;T
Sift4G
Benign
0.25
T;T
Polyphen
0.0010
B;B
Vest4
0.016
MPC
0.053
ClinPred
0.0096
T
GERP RS
-3.2
Varity_R
0.11
gMVP
0.14

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.

Other links and lift over

dbSNP: rs4833095; hg19: chr4-38799710; COSMIC: COSV58303357; COSMIC: COSV58303357; API