rs5743828

Positions:

• chr4-38825899-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508254.6(TLR6):​c.*1184G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,452 control chromosomes in the GnomAD database, including 3,994 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 (3988 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: TLR6 ENST00000508254.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR6	NM_006068.5	c.*1184G>A		3_prime_UTR_variant	2/2	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.*1184G>A		3_prime_UTR_variant	2/2	1	NM_006068.5	ENSP00000424718	P1
TLR1	ENST00000506146.5	c.-352-20706G>A		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30758 AN: 151940 Hom.: 3984 Cov.: 32

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.137 AC: 54 AN: 394 Hom.: 6 Cov.: 0 AF XY: 0.158 AC XY: 32 AN XY: 202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.0385

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.202 AC: 30777 AN: 152058 Hom.: 3988 Cov.: 32 AF XY: 0.199 AC XY: 14799 AN XY: 74306

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.168

Alfa AF: 0.248 Hom.: 816

Bravo AF: 0.180

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.46
DANN	Benign	0.71

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: rs5743828; hg19: chr4-38827520;