4-38846296-T-C

Variant names:

• chr4-38846296-T-C
• rs6531673
• NM_006068.5:c.-65+10465A>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.-65+10465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,908 control chromosomes in the GnomAD database, including 27,943 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 0.59 (27943 hom., cov: 31)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	NM_006068.5	MANE Select	c.-65+10465A>G		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-65+11392A>G		intron	N/A	NP_001381482.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.-65+10465A>G		intron	N/A	ENSP00000424718.2
	TLR6	ENST00000381950.2	TSL:6	c.-217-2505A>G		intron	N/A	ENSP00000371376.1
	TLR1	ENST00000506146.5	TSL:4	c.-353+10465A>G		intron	N/A	ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89861 AN: 151790 Hom.: 27901 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.592 AC: 89962 AN: 151908 Hom.: 27943 Cov.: 31 AF XY: 0.589 AC XY: 43716 AN XY: 74232

African (AFR) AF: 0.787 AC: 32624 AN: 41446

American (AMR) AF: 0.531 AC: 8109 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2180 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3693 AN: 5180

South Asian (SAS) AF: 0.534 AC: 2574 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4844 AN: 10474

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34043 AN: 67952

Other (OTH) AF: 0.604 AC: 1273 AN: 2108

Alfa AF: 0.534 Hom.: 95638

Bravo AF: 0.606

Asia WGS AF: 0.631 AC: 2194 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		0.13
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: rs6531673; hg19: chr4-38847917;