rs5743611

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003263.4(TLR1):c.239G>C(p.Arg80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,613,772 control chromosomes in the GnomAD database, including 7,073 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.069 ( 790 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6283 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.117

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]

TLR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002158165).

BP6

Variant 4-38798593-C-G is Benign according to our data. Variant chr4-38798593-C-G is described in ClinVar as [Benign]. Clinvar id is 3037177.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.239G>C	p.Arg80Thr	missense_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 link	c.239G>C	p.Arg80Thr	missense_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2		Q15399

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10523

AN:

152044

Hom.:

790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0417

GnomAD3 exomes

AF:

0.0694

AC:

17406

AN:

250914

Hom.:

1152

AF XY:

0.0683

AC XY:

9261

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.0933

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0805

AC:

117604

AN:

1461610

Hom.:

6283

Cov.:

AF XY:

0.0791

AC XY:

57502

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0442

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00332

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.0891

Gnomad4 OTH exome

AF:

0.0667

GnomAD4 genome

AF:

0.0692

AC:

10522

AN:

152162

Hom.:

790

Cov.:

AF XY:

0.0718

AC XY:

5341

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0413

Alfa

AF:

0.0852

Hom.:

558

Bravo

AF:

0.0492

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0737

AC:

284

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0908

AC:

781

ExAC

AF:

0.0687

AC:

8341

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0850

EpiControl

AF:

0.0767

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR1-related disorder

Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.066

T;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.84

T;.;D;D

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.042

D;D;D;D

Sift4G

Benign

0.46

T;T;T;.

Polyphen

0.13

B;B;.;.

Vest4

0.11

MPC

0.12

ClinPred

0.014

GERP RS

3.2

Varity_R

0.35

gMVP

0.23

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