rs1039559

Variant names:

• chr4-38829975-G-A
• rs1039559
• NM_006068.5:c.-64-438C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-38829975-G-A
• chr4-38829975-G-C
• chr4-38829975-G-T

Variant summary

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

The NM_006068.5(TLR6):​c.-64-438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,108 control chromosomes in the GnomAD database, including 30,349 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 0.62 (30349 hom., cov: 33)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 38 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006068.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	NM_006068.5	MANE Select	c.-64-438C>T		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-64-438C>T		intron	N/A	NP_001381482.1	Q9Y2C9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.-64-438C>T		intron	N/A	ENSP00000424718.2	Q9Y2C9-1
	TLR6	ENST00000381950.2	TSL:6	c.-64-438C>T		intron	N/A	ENSP00000371376.1	Q9Y2C9-1
	TLR6	ENST00000966018.1		c.-64-438C>T		intron	N/A	ENSP00000636077.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93842 AN: 151990 Hom.: 30310 Cov.: 33

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.618 AC: 93936 AN: 152108 Hom.: 30349 Cov.: 33 AF XY: 0.615 AC XY: 45723 AN XY: 74352

African (AFR) AF: 0.808 AC: 33522 AN: 41494

American (AMR) AF: 0.534 AC: 8155 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2279 AN: 3472

East Asian (EAS) AF: 0.730 AC: 3785 AN: 5182

South Asian (SAS) AF: 0.587 AC: 2832 AN: 4828

European-Finnish (FIN) AF: 0.499 AC: 5272 AN: 10562

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36076 AN: 67972

Other (OTH) AF: 0.640 AC: 1351 AN: 2112

Alfa AF: 0.569 Hom.: 80692

Bravo AF: 0.628

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.27
PhyloP100		-0.013
PromoterAI		0.0028	Neutral
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: rs1039559; hg19: chr4-38831596;