rs5743818

Variant names:

• chr4-38827542-A-C
• rs5743818
• NM_006068.5:c.1932T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-38827542-A-C
• chr4-38827542-A-T

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.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
• Publications: 37 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.1932T>G	p.Ala644Ala	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.1932T>G	p.Ala644Ala	synonymous_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.1932T>G	p.Ala644Ala	synonymous_variant	Exon 3 of 3	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-352-22349T>G		intron_variant	Intron 1 of 5	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

GnomAD2 exomes AF: 0.192 AC: 48312 AN: 251464 AF XY: 0.193

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 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

African (AFR) AF: 0.0718 AC: 2405 AN: 33480

American (AMR) AF: 0.0818 AC: 3658 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4870 AN: 26134

East Asian (EAS) AF: 0.0115 AC: 455 AN: 39700

South Asian (SAS) AF: 0.106 AC: 9178 AN: 86258

European-Finnish (FIN) AF: 0.350 AC: 18673 AN: 53418

Middle Eastern (MID) AF: 0.0988 AC: 570 AN: 5768

European-Non Finnish (NFE) AF: 0.275 AC: 305685 AN: 1111996

Other (OTH) AF: 0.220 AC: 13311 AN: 60396

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

African (AFR) AF: 0.0756 AC: 3140 AN: 41548

American (AMR) AF: 0.0969 AC: 1482 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5178

South Asian (SAS) AF: 0.0915 AC: 441 AN: 4822

European-Finnish (FIN) AF: 0.361 AC: 3813 AN: 10552

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19033 AN: 67990

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.228 Hom.: 8148

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
PhyloP100		-2.1
Mutation Taster		=99/1	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: rs5743818; hg19: chr4-38829163; COSMIC: COSV67935193; COSMIC: COSV67935193;