rs5743818

Positions:

• chr4-38827542-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006068.5(TLR6):​c.1932T>G​(p.Ala644Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,614,050 control chromosomes in the GnomAD database, including 52,605 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 0.19 (3821 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48784 hom.)
• Consequence: TLR6 NM_006068.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-2.13 with no splicing effect.
• 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/exons	MANE	Protein	UniProt
TLR6	NM_006068.5	c.1932T>G	p.Ala644Ala	synonymous_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.1932T>G	p.Ala644Ala	synonymous_variant	2/2	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.1932T>G	p.Ala644Ala	synonymous_variant	3/3	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-352-22349T>G		intron_variant		4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29103 AN: 152058 Hom.: 3821 Cov.: 32

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.192 AC: 48312 AN: 251464 Hom.: 6221 AF XY: 0.193 AC XY: 26288 AN XY: 135910

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.0768

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0122

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.245 AC: 358805 AN: 1461874 Hom.: 48784 Cov.: 36 AF XY: 0.242 AC XY: 176285 AN XY: 727244

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.0818

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.191 AC: 29107 AN: 152176 Hom.: 3821 Cov.: 32 AF XY: 0.188 AC XY: 13979 AN XY: 74370

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.0969

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.158

Alfa AF: 0.237 Hom.: 6309

Bravo AF: 0.168

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.261

EpiControl AF: 0.243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.43

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: rs5743818; hg19: chr4-38829163; COSMIC: COSV67935193; COSMIC: COSV67935193;