rs5743820

Positions:

chr4-38827207-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000508254.6(TLR6):c.2267C>T(p.Thr756Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,614,166 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0078 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 165 hom. )

Consequence

TLR6
ENST00000508254.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.841

Variant links:

Genes affected

TLR6 (HGNC:16711): (toll like receptor 6) 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 receptor functionally interacts with toll-like receptor 2 to mediate cellular response to bacterial lipoproteins. A Ser249Pro polymorphism in the extracellular domain of the encoded protein may be associated with an increased of asthma is some populations.[provided by RefSeq, Jan 2011]

TLR6 links:

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=0.0028704405).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00776 (1181/152284) while in subpopulation SAS AF= 0.0267 (129/4828). AF 95% confidence interval is 0.023. There are 5 homozygotes in gnomad4. There are 579 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR6	NM_006068.5 linkuse as main transcript	c.2267C>T	p.Thr756Met	missense_variant	2/2	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6 linkuse as main transcript	c.2267C>T	p.Thr756Met	missense_variant	2/2	1	NM_006068.5	ENSP00000424718	P1	Q9Y2C9-1
TLR6	ENST00000381950.2 linkuse as main transcript	c.2267C>T	p.Thr756Met	missense_variant	3/3			ENSP00000371376	P1	Q9Y2C9-1
TLR1	ENST00000506146.5 linkuse as main transcript	c.-352-22014C>T		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1185

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0286

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.00888

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0112

AC:

2824

AN:

251486

Hom.:

AF XY:

0.0132

AC XY:

1799

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00760

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.00935

AC:

13673

AN:

1461882

Hom.:

165

Cov.:

AF XY:

0.0105

AC XY:

7666

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.00800

Gnomad4 ASJ exome

AF:

0.0265

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00770

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00776

AC:

1181

AN:

152284

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

579

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.0286

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00888

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00758

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.0115

AC:

1395

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0138

EpiControl

AF:

0.0147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.059

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.30

T;.;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.18

Sift

Benign

0.033

D;D;.

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.15

B;B;.

Vest4

0.030

MPC

0.19

ClinPred

0.0056

GERP RS

2.3

Varity_R

0.036

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over