rs2381289

Variant names:

• chr4-38825250-G-A
• rs2381289
• NM_006068.5:c.*1833C>T

Variant summary

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

The NM_006068.5(TLR6):​c.*1833C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,008 control chromosomes in the GnomAD database, including 14,078 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 0.41 (14078 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.*1833C>T		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.*1833C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR1	ENST00000506146.5	c.-352-20057C>T		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62917 AN: 151884 Hom.: 14065 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.414 AC: 62970 AN: 152002 Hom.: 14078 Cov.: 32 AF XY: 0.411 AC XY: 30491 AN XY: 74270

African (AFR) AF: 0.262 AC: 10868 AN: 41448

American (AMR) AF: 0.333 AC: 5090 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1883 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2309 AN: 5168

South Asian (SAS) AF: 0.407 AC: 1963 AN: 4822

European-Finnish (FIN) AF: 0.486 AC: 5112 AN: 10514

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34176 AN: 67980

Other (OTH) AF: 0.456 AC: 964 AN: 2112

Alfa AF: 0.451 Hom.: 7972

Bravo AF: 0.397

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		0.15
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: rs2381289; hg19: chr4-38826871;