chr4-38855689-G-A

Variant names:

• chr4-38855689-G-A
• rs17429224
• NM_006068.5:c.-65+1072C>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.-65+1072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,922 control chromosomes in the GnomAD database, including 4,917 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 0.24 (4917 hom., cov: 31)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 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+1072C>T		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-65+1999C>T		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+1072C>T		intron	N/A	ENSP00000424718.2
	TLR6	ENST00000381950.2	TSL:6	c.-218+1072C>T		intron	N/A	ENSP00000371376.1
	TLR1	ENST00000506146.5	TSL:4	c.-353+1072C>T		intron	N/A	ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36562 AN: 151804 Hom.: 4904 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.241 AC: 36609 AN: 151922 Hom.: 4917 Cov.: 31 AF XY: 0.238 AC XY: 17664 AN XY: 74226

African (AFR) AF: 0.215 AC: 8903 AN: 41416

American (AMR) AF: 0.120 AC: 1836 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3466

East Asian (EAS) AF: 0.134 AC: 694 AN: 5182

South Asian (SAS) AF: 0.148 AC: 712 AN: 4812

European-Finnish (FIN) AF: 0.374 AC: 3931 AN: 10508

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19262 AN: 67952

Other (OTH) AF: 0.209 AC: 440 AN: 2106

Alfa AF: 0.259 Hom.: 20604

Bravo AF: 0.220

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.30
PhyloP100		0.0050
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: rs17429224; hg19: chr4-38857310;