rs35220466

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006068.5(TLR6):c.740G>A(p.Arg247Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,613,838 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 8 hom. )

Consequence

TLR6
NM_006068.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003818214).

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000506 (739/1461528) while in subpopulation AFR AF = 0.0163 (546/33464). AF 95% confidence interval is 0.0152. There are 8 homozygotes in GnomAdExome4. There are 350 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5 link	c.740G>A	p.Arg247Lys	missense_variant	Exon 2 of 2	ENST00000508254.6	NP_006059.2	Q9Y2C9-1B2R933

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLR6	ENST00000508254.6 link	c.740G>A	p.Arg247Lys	missense_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2	Q9Y2C9-1D6RAV7
TLR6	ENST00000381950.2 link	c.740G>A	p.Arg247Lys	missense_variant	Exon 3 of 3	6		ENSP00000371376.1	Q9Y2C9-1
TLR1	ENST00000506146.5 link	c.-352-23541G>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1	D6RCE8

Frequencies

GnomAD3 genomes

AF:

0.00430

AC:

654

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00111

AC:

278

AN:

250730

AF XY:

0.000833

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000506

AC:

739

AN:

1461528

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

350

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.0163

AC:

546

AN:

33464

American (AMR)

AF:

0.000783

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111870

Other (OTH)

AF:

0.00126

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00429

AC:

654

AN:

152310

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0146

AC:

605

AN:

41550

American (AMR)

AF:

0.00216

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00489

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00138

AC:

168

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.0

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.037

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.66

T;.;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.67

N;N;N

PhyloP100

0.20

PrimateAI

Benign

0.23

PROVEAN

Benign

0.61

N;N;.

REVEL

Benign

0.073

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.054

MVP

0.21

MPC

0.15

ClinPred

0.0044

GERP RS

3.6

Varity_R

0.022

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over