rs5743823

Positions:

• chr4-38827028-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006068.5(TLR6):​c.*55T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,356,248 control chromosomes in the GnomAD database, including 79 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 0.0077 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (73 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00771 (1174/152350) while in subpopulation SAS AF= 0.0381 (184/4826). AF 95% confidence interval is 0.0336. There are 6 homozygotes in gnomad4. There are 602 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR6	NM_006068.5	c.*55T>C		3_prime_UTR_variant	2/2	ENST00000508254.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR6	ENST00000508254.6	c.*55T>C		3_prime_UTR_variant	2/2	1	NM_006068.5	P1
TLR6	ENST00000381950.2	c.*55T>C		3_prime_UTR_variant	3/3			P1
TLR1	ENST00000506146.5	c.-352-21835T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1174 AN: 152232 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.00764

GnomAD4 exome AF: 0.00637 AC: 7672 AN: 1203898 Hom.: 73 Cov.: 17 AF XY: 0.00714 AC XY: 4241 AN XY: 593876

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.00630

Gnomad4 ASJ exome AF: 0.00353

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.0343

Gnomad4 FIN exome AF: 0.00125

Gnomad4 NFE exome AF: 0.00420

Gnomad4 OTH exome AF: 0.00764

GnomAD4 genome AF: 0.00771 AC: 1174 AN: 152350 Hom.: 6 Cov.: 33 AF XY: 0.00808 AC XY: 602 AN XY: 74498

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.00974

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00867

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00462

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00596 Hom.: 0

Bravo AF: 0.00797

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.42

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: rs5743823; hg19: chr4-38828649;