Genetic Variant TLR6:c.*849G>A (chr4-38826234-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006068.5(TLR6):c.*849G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,334 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 147 hom., cov: 33)

Exomes 𝑓: 0.050 ( 0 hom. )

Consequence

TLR6
NM_006068.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.656

Publications

1 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5 link	c.*849G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000508254.6	NP_006059.2	Q9Y2C9-1B2R933

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6 link	c.*849G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2		Q9Y2C9-1D6RAV7
TLR1	ENST00000506146.5 link	c.-352-21041G>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1		D6RCE8

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5197

AN:

152182

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0454

GnomAD4 exome

AF:

0.0500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0342

AC:

5202

AN:

152294

Hom.:

147

Cov.:

AF XY:

0.0339

AC XY:

2523

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0735

AC:

3053

AN:

41550

American (AMR)

AF:

0.0280

AC:

428

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

151

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0501

AC:

242

AN:

4826

European-Finnish (FIN)

AF:

0.00678

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0164

AC:

1116

AN:

68018

Other (OTH)

AF:

0.0435

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

255

510

766

1021

1276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0284

Hom.:

Bravo

AF:

0.0373

Asia WGS

AF:

0.0330

AC:

115

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

(source)

DANN

Benign

0.74

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over