rs3775073

Variant names:

• chr4-38828211-T-C
• rs3775073
• NM_006068.5:c.1263A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-38828211-T-C
• chr4-38828211-T-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.1263A>G​(p.Lys421Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,613,206 control chromosomes in the GnomAD database, including 106,819 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 0.44 (16127 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90692 hom.)
• Consequence: TLR6 NM_006068.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 48 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=-0.99).
• BP7: Synonymous conserved (PhyloP=-0.978 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006068.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	NM_006068.5	MANE Select	c.1263A>G	p.Lys421Lys	synonymous	Exon 2 of 2	NP_006059.2
	TLR6	NM_001394553.1		c.1263A>G	p.Lys421Lys	synonymous	Exon 2 of 2	NP_001381482.1	Q9Y2C9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.1263A>G	p.Lys421Lys	synonymous	Exon 2 of 2	ENSP00000424718.2	Q9Y2C9-1
	TLR6	ENST00000381950.2	TSL:6	c.1263A>G	p.Lys421Lys	synonymous	Exon 3 of 3	ENSP00000371376.1	Q9Y2C9-1
	TLR6	ENST00000966018.1		c.1263A>G	p.Lys421Lys	synonymous	Exon 2 of 2	ENSP00000636077.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66178 AN: 151930 Hom.: 16096 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.372 AC: 93513 AN: 251194 AF XY: 0.366

Gnomad AFR exome AF: 0.675

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.347 AC: 506652 AN: 1461158 Hom.: 90692 Cov.: 49 AF XY: 0.347 AC XY: 252305 AN XY: 726760

African (AFR) AF: 0.675 AC: 22564 AN: 33450

American (AMR) AF: 0.323 AC: 14437 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8690 AN: 26128

East Asian (EAS) AF: 0.340 AC: 13499 AN: 39684

South Asian (SAS) AF: 0.376 AC: 32433 AN: 86228

European-Finnish (FIN) AF: 0.404 AC: 21596 AN: 53408

Middle Eastern (MID) AF: 0.333 AC: 1919 AN: 5764

European-Non Finnish (NFE) AF: 0.332 AC: 368924 AN: 1111442

Other (OTH) AF: 0.374 AC: 22590 AN: 60364

GnomAD4 genome AF: 0.436 AC: 66262 AN: 152048 Hom.: 16127 Cov.: 32 AF XY: 0.436 AC XY: 32385 AN XY: 74318

African (AFR) AF: 0.663 AC: 27457 AN: 41444

American (AMR) AF: 0.339 AC: 5185 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1976 AN: 5156

South Asian (SAS) AF: 0.369 AC: 1779 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4391 AN: 10566

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23211 AN: 67976

Other (OTH) AF: 0.404 AC: 853 AN: 2114

Alfa AF: 0.371 Hom.: 34762

Bravo AF: 0.436

Asia WGS AF: 0.440 AC: 1529 AN: 3478

EpiCase AF: 0.336

EpiControl AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.63
PhyloP100		-0.98
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: rs3775073; hg19: chr4-38829832; COSMIC: COSV67935197; COSMIC: COSV67935197;