chr4-38867279-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0142

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.174

Alfa AF: 0.234 Hom.: 1649

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17429273; hg19: chr4-38868900;