4-38831586-C-G

Variant names:

• chr4-38831586-C-G
• rs5743788
• NM_006068.5:c.-64-2049G>C

Variant summary

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

The NM_006068.5(TLR6):​c.-64-2049G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,944 control chromosomes in the GnomAD database, including 24,561 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 0.56 (24561 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-2049G>C		intron_variant	Intron 1 of 1	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.-64-2049G>C		intron_variant	Intron 1 of 1	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-64-2049G>C		intron_variant	Intron 2 of 2	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-353+25175G>C		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85275 AN: 151828 Hom.: 24539 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.562 AC: 85347 AN: 151944 Hom.: 24561 Cov.: 32 AF XY: 0.560 AC XY: 41559 AN XY: 74258

African (AFR) AF: 0.675 AC: 27980 AN: 41466

American (AMR) AF: 0.501 AC: 7651 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3777 AN: 5182

South Asian (SAS) AF: 0.574 AC: 2763 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4851 AN: 10518

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34245 AN: 67912

Other (OTH) AF: 0.586 AC: 1235 AN: 2106

Alfa AF: 0.407 Hom.: 1077

Bravo AF: 0.568

Asia WGS AF: 0.655 AC: 2274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.28
PhyloP100		0.074
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: rs5743788; hg19: chr4-38833207;