chr4-38830438-G-A

Variant names:

• chr4-38830438-G-A
• rs5743805
• NM_006068.5:c.-64-901C>T

Variant summary

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

The NM_006068.5(TLR6):​c.-64-901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,102 control chromosomes in the GnomAD database, including 2,205 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 0.12 (2205 hom., cov: 33)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 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.-64-901C>T		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-64-901C>T		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.-64-901C>T		intron	N/A	ENSP00000424718.2	Q9Y2C9-1
	TLR6	ENST00000381950.2	TSL:6	c.-64-901C>T		intron	N/A	ENSP00000371376.1	Q9Y2C9-1
	TLR6	ENST00000966018.1		c.-64-901C>T		intron	N/A	ENSP00000636077.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18987 AN: 151984 Hom.: 2209 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.125 AC: 18998 AN: 152102 Hom.: 2205 Cov.: 33 AF XY: 0.129 AC XY: 9594 AN XY: 74358

African (AFR) AF: 0.277 AC: 11497 AN: 41460

American (AMR) AF: 0.172 AC: 2619 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5176

South Asian (SAS) AF: 0.179 AC: 861 AN: 4820

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10596

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.0266 AC: 1809 AN: 67998

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.0229 Hom.: 29

Bravo AF: 0.141

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.23
PhyloP100		-0.12
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: rs5743805; hg19: chr4-38832059;