4-38842128-G-C

Variant names:

• chr4-38842128-G-C
• rs7665774
• NM_006068.5:c.-64-12591C>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.-64-12591C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,870 control chromosomes in the GnomAD database, including 29,762 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 0.61 (29762 hom., cov: 30)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-12591C>G		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.-64-12591C>G		intron_variant	Intron 1 of 1	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-65+1511C>G		intron_variant	Intron 2 of 2	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-353+14633C>G		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93002 AN: 151750 Hom.: 29720 Cov.: 30

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.613 AC: 93105 AN: 151870 Hom.: 29762 Cov.: 30 AF XY: 0.610 AC XY: 45282 AN XY: 74194

African (AFR) AF: 0.798 AC: 33057 AN: 41436

American (AMR) AF: 0.551 AC: 8409 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3470

East Asian (EAS) AF: 0.724 AC: 3734 AN: 5156

South Asian (SAS) AF: 0.546 AC: 2617 AN: 4796

European-Finnish (FIN) AF: 0.497 AC: 5237 AN: 10532

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35804 AN: 67912

Other (OTH) AF: 0.635 AC: 1341 AN: 2112

Alfa AF: 0.584 Hom.: 3182

Bravo AF: 0.626

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		0.013
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: rs7665774; hg19: chr4-38843749;