chr4-38831533-T-C

Variant names:

• chr4-38831533-T-C
• rs5743790
• NM_006068.5:c.-64-1996A>G

Variant summary

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

The NM_006068.5(TLR6):​c.-64-1996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,002 control chromosomes in the GnomAD database, including 13,702 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 0.40 (13702 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 0 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 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.-64-1996A>G		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-64-1996A>G		intron	N/A	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.-64-1996A>G		intron	N/A	ENSP00000424718.2	Q9Y2C9-1
	TLR6	ENST00000381950.2	TSL:6	c.-64-1996A>G		intron	N/A	ENSP00000371376.1	Q9Y2C9-1
	TLR6	ENST00000966018.1		c.-64-1996A>G		intron	N/A	ENSP00000636077.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61090 AN: 151884 Hom.: 13682 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61159 AN: 152002 Hom.: 13702 Cov.: 32 AF XY: 0.402 AC XY: 29891 AN XY: 74286

African (AFR) AF: 0.608 AC: 25191 AN: 41440

American (AMR) AF: 0.314 AC: 4802 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3464

East Asian (EAS) AF: 0.383 AC: 1985 AN: 5186

South Asian (SAS) AF: 0.356 AC: 1712 AN: 4812

European-Finnish (FIN) AF: 0.380 AC: 4002 AN: 10536

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21394 AN: 67958

Other (OTH) AF: 0.361 AC: 764 AN: 2114

Alfa AF: 0.366 Hom.: 2265

Bravo AF: 0.403

Asia WGS AF: 0.430 AC: 1494 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		0.056
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: rs5743790; hg19: chr4-38833154;