4-38828391-G-C

Variant names:

• chr4-38828391-G-C
• rs3821985
• NM_006068.5:c.1083C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006068.5(TLR6):​c.1083C>G​(p.Thr361Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,612,288 control chromosomes in the GnomAD database, including 105,146 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 0.43 (15381 hom., cov: 33)
  • Exomes 𝑓: 0.35 (89765 hom.)
• Consequence: TLR6 NM_006068.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 41 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.1083C>G	p.Thr361Thr	synonymous_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.1083C>G	p.Thr361Thr	synonymous_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.1083C>G	p.Thr361Thr	synonymous_variant	Exon 3 of 3	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-352-23198C>G		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65011 AN: 151972 Hom.: 15355 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.389

GnomAD2 exomes AF: 0.370 AC: 92817 AN: 250914 AF XY: 0.364

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.320

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.346 AC: 504804 AN: 1460198 Hom.: 89765 Cov.: 38 AF XY: 0.346 AC XY: 251376 AN XY: 726034

African (AFR) AF: 0.642 AC: 21468 AN: 33460

American (AMR) AF: 0.321 AC: 14343 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8687 AN: 26122

East Asian (EAS) AF: 0.340 AC: 13483 AN: 39642

South Asian (SAS) AF: 0.376 AC: 32410 AN: 86210

European-Finnish (FIN) AF: 0.404 AC: 21587 AN: 53390

Middle Eastern (MID) AF: 0.327 AC: 1884 AN: 5768

European-Non Finnish (NFE) AF: 0.332 AC: 368523 AN: 1110606

Other (OTH) AF: 0.372 AC: 22419 AN: 60326

GnomAD4 genome AF: 0.428 AC: 65087 AN: 152090 Hom.: 15381 Cov.: 33 AF XY: 0.428 AC XY: 31848 AN XY: 74334

African (AFR) AF: 0.635 AC: 26346 AN: 41492

American (AMR) AF: 0.336 AC: 5141 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1979 AN: 5172

South Asian (SAS) AF: 0.369 AC: 1780 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4400 AN: 10552

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23207 AN: 67976

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.297 Hom.: 1246

Bravo AF: 0.427

EpiCase AF: 0.335

EpiControl AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		-1.8
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: rs3821985; hg19: chr4-38830012; COSMIC: COSV67935227; COSMIC: COSV67935227;