chr4-38827207-G-A

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.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. 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 0.0078 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 165 hom. )

Consequence

TLR6
NM_006068.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.841

Publications

13 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=0.0028704405).

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5 link	c.2267C>T	p.Thr756Met	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.2267C>T	p.Thr756Met	missense_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2	Q9Y2C9-1D6RAV7
TLR6	ENST00000381950.2 link	c.2267C>T	p.Thr756Met	missense_variant	Exon 3 of 3	6		ENSP00000371376.1	Q9Y2C9-1
TLR1	ENST00000506146.5 link	c.-352-22014C>T		intron_variant	Intron 1 of 5	4		ENSP00000423725.1	D6RCE8

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

GnomAD2 exomes

AF:

0.0112

AC:

2824

AN:

251486

AF XY:

0.0132

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 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

African (AFR)

AF:

0.00281

AC:

AN:

33480

American (AMR)

AF:

0.00800

AC:

358

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

692

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0326

AC:

2815

AN:

86258

European-Finnish (FIN)

AF:

0.00206

AC:

110

AN:

53420

Middle Eastern (MID)

AF:

0.0548

AC:

316

AN:

5768

European-Non Finnish (NFE)

AF:

0.00770

AC:

8566

AN:

1112000

Other (OTH)

AF:

0.0119

AC:

717

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

768

1537

2305

3074

3842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.00776

AC:

1181

AN:

152284

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

579

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00301

AC:

125

AN:

41546

American (AMR)

AF:

0.00856

AC:

131

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0286

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.0267

AC:

129

AN:

4828

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00888

AC:

604

AN:

68026

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0101

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

(source)

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;.

PhyloP100

0.84

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

Mutation Taster

=96/4

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