rs17429273

Variant names:

• chr4-38867279-A-G
• rs17429273
• XM_047449498.1:c.-65+647T>C

Variant summary

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

The XM_047449498.1(TLR6):​c.-65+647T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,214 control chromosomes in the GnomAD database, including 3,995 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 0.20 (3995 hom., cov: 32)
• Consequence: TLR6 XM_047449498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	XM_047449498.1	c.-65+647T>C		intron_variant	Intron 1 of 1		XP_047305454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31125 AN: 152096 Hom.: 3993 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.205 AC: 31133 AN: 152214 Hom.: 3995 Cov.: 32 AF XY: 0.201 AC XY: 14932 AN XY: 74410

African (AFR) AF: 0.122 AC: 5087 AN: 41546

American (AMR) AF: 0.103 AC: 1572 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.0142 AC: 74 AN: 5194

South Asian (SAS) AF: 0.0921 AC: 445 AN: 4830

European-Finnish (FIN) AF: 0.352 AC: 3726 AN: 10574

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19069 AN: 67984

Other (OTH) AF: 0.174 AC: 367 AN: 2114

Alfa AF: 0.232 Hom.: 1976

Bravo AF: 0.183

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.41
PhyloP100		-0.40
PromoterAI		0.021	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17429273; hg19: chr4-38868900;