rs5743789

Variant names:

• chr4-38831552-A-T
• rs5743789
• NM_006068.5:c.-64-2015T>A

Variant summary

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

The NM_006068.5(TLR6):​c.-64-2015T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,248 control chromosomes in the GnomAD database, including 2,303 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 0.15 (2303 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-2015T>A		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.-64-2015T>A		intron_variant	Intron 1 of 1	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-64-2015T>A		intron_variant	Intron 2 of 2	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-353+25209T>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22818 AN: 152130 Hom.: 2304 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.150 AC: 22813 AN: 152248 Hom.: 2303 Cov.: 32 AF XY: 0.148 AC XY: 11038 AN XY: 74432

African (AFR) AF: 0.0359 AC: 1494 AN: 41570

American (AMR) AF: 0.183 AC: 2793 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1793 AN: 5182

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4826

European-Finnish (FIN) AF: 0.0811 AC: 861 AN: 10612

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12839 AN: 67990

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.158 Hom.: 321

Bravo AF: 0.155

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.76
PhyloP100		1.1
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: rs5743789; hg19: chr4-38833173;