rs5743618

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003263.4(TLR1):c.1805G>T(p.Ser602Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,828 control chromosomes in the GnomAD database, including 158,240 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 Conflicting classifications of pathogenicity,protective (no stars).

Frequency

Genomes: 𝑓 0.52 ( 27664 hom., cov: 32)

Exomes 𝑓: 0.35 ( 130576 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity; protective no assertion criteria provided B:2O:1

Conservation

PhyloP100: 0.245

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5470836E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4 linkuse as main transcript	c.1805G>T	p.Ser602Ile	missense_variant	4/4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TLR1	ENST00000308979.7 linkuse as main transcript	c.1805G>T	p.Ser602Ile	missense_variant	4/4	1	NM_003263.4	ENSP00000354932	P1
TLR1	ENST00000502213.6 linkuse as main transcript	c.1805G>T	p.Ser602Ile	missense_variant	3/3	1		ENSP00000421259	P1
TLR1	ENST00000505744.5 linkuse as main transcript	n.235+3830G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79419

AN:

151982

Hom.:

27592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.906

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.529

AC:

132776

AN:

251036

Hom.:

46587

AF XY:

0.530

AC XY:

71913

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.524

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.896

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.488

GnomAD4 exome

AF:

0.348

AC:

508406

AN:

1461726

Hom.:

130576

Cov.:

AF XY:

0.364

AC XY:

264348

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.888

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.893

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.523

AC:

79556

AN:

152102

Hom.:

27664

Cov.:

AF XY:

0.531

AC XY:

39486

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.868

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.538

Gnomad4 EAS

AF:

0.988

Gnomad4 SAS

AF:

0.906

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.404

Hom.:

3210

Bravo

AF:

0.573

ESP6500AA

AF:

0.850

AC:

3744

ESP6500EA

AF:

0.288

AC:

2480

ExAC

AF:

0.539

AC:

65450

ClinVar

Significance: Conflicting classifications of pathogenicity; protective

Submissions summary: Benign:2Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Leprosy, protection against

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 01, 2012

- -

TLR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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). -

Leprosy, susceptibility to, 1

Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.0

DANN

Benign

0.11

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.054

T;.

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.5

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.056

Sift

Benign

1.0

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

B;B

Vest4

0.015

MPC

0.073

ClinPred

0.0037

GERP RS

2.8

Varity_R

0.053

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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