rs1039559

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR6	NM_006068.5	c.-64-438C>T		intron_variant		ENST00000508254.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR6	ENST00000508254.6	c.-64-438C>T		intron_variant		1	NM_006068.5	P1
TLR6	ENST00000381950.2	c.-64-438C>T		intron_variant				P1
TLR1	ENST00000506146.5	c.-352-24782C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.640

Alfa AF: 0.556 Hom.: 48412

Bravo AF: 0.628

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.27

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

LitVar

Other links and lift over

dbSNP: rs1039559; hg19: chr4-38831596;