rs5743827

Variant names:

• chr4-38825904-C-T
• rs5743827
• NM_006068.5:c.*1179G>A

Variant summary

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

The NM_006068.5(TLR6):​c.*1179G>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 0.263 in 152,410 control chromosomes in the GnomAD database, including 5,820 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 0.26 (5814 hom., cov: 32)
  • Exomes 𝑓: 0.18 (6 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 7 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]

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.*1179G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.*1179G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR1	ENST00000506146.5	c.-352-20711G>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39942 AN: 151912 Hom.: 5799 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.175 AC: 67 AN: 382 Hom.: 6 Cov.: 0 AF XY: 0.175 AC XY: 35 AN XY: 200

African (AFR) AF: 0.250 AC: 3 AN: 12

American (AMR) AF: 0.0714 AC: 1 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1 AN: 16

East Asian (EAS) AF: 0.0926 AC: 5 AN: 54

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.357 AC: 15 AN: 42

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.185 AC: 41 AN: 222

Other (OTH) AF: 0.0455 AC: 1 AN: 22

GnomAD4 genome AF: 0.263 AC: 40000 AN: 152028 Hom.: 5814 Cov.: 32 AF XY: 0.261 AC XY: 19350 AN XY: 74280

African (AFR) AF: 0.226 AC: 9367 AN: 41528

American (AMR) AF: 0.150 AC: 2287 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 719 AN: 3464

East Asian (EAS) AF: 0.0993 AC: 515 AN: 5184

South Asian (SAS) AF: 0.189 AC: 911 AN: 4816

European-Finnish (FIN) AF: 0.401 AC: 4217 AN: 10516

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.313 AC: 21249 AN: 67918

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.309 Hom.: 1047

Bravo AF: 0.241

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743827; hg19: chr4-38827525;