rs5743806

Variant names:

• chr4-38830146-A-G
• rs5743806
• NM_006068.5:c.-64-609T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006068.5(TLR6):​c.-64-609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,084 control chromosomes in the GnomAD database, including 13,709 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 0.40 (13709 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 15 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-609T>C		intron_variant	Intron 1 of 1	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.-64-609T>C		intron_variant	Intron 1 of 1	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-64-609T>C		intron_variant	Intron 2 of 2	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-352-24953T>C		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61114 AN: 151966 Hom.: 13689 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61183 AN: 152084 Hom.: 13709 Cov.: 32 AF XY: 0.402 AC XY: 29919 AN XY: 74338

African (AFR) AF: 0.608 AC: 25192 AN: 41466

American (AMR) AF: 0.314 AC: 4809 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1036 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1978 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4828

European-Finnish (FIN) AF: 0.380 AC: 4009 AN: 10560

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21407 AN: 67974

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.393 Hom.: 1705

Bravo AF: 0.403

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743806; hg19: chr4-38831767;