chr4-38831401-A-G

Variant names:

• chr4-38831401-A-G
• rs5743792
• NM_006068.5:c.-64-1864T>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.-64-1864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,204 control chromosomes in the GnomAD database, including 2,291 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 0.13 (2291 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 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.-64-1864T>C		intron	N/A	NP_006059.2
	TLR6	NM_001394553.1		c.-64-1864T>C		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.-64-1864T>C		intron	N/A	ENSP00000424718.2
	TLR6	ENST00000381950.2	TSL:6	c.-64-1864T>C		intron	N/A	ENSP00000371376.1
	TLR1	ENST00000506146.5	TSL:4	c.-353+25360T>C		intron	N/A	ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19327 AN: 152086 Hom.: 2295 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.127 AC: 19339 AN: 152204 Hom.: 2291 Cov.: 32 AF XY: 0.131 AC XY: 9740 AN XY: 74442

African (AFR) AF: 0.286 AC: 11865 AN: 41484

American (AMR) AF: 0.173 AC: 2642 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1424 AN: 5178

South Asian (SAS) AF: 0.178 AC: 856 AN: 4822

European-Finnish (FIN) AF: 0.0129 AC: 137 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1812 AN: 68026

Other (OTH) AF: 0.124 AC: 263 AN: 2116

Alfa AF: 0.0786 Hom.: 144

Bravo AF: 0.144

Asia WGS AF: 0.231 AC: 801 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.50
PhyloP100		1.4
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: rs5743792; hg19: chr4-38833022;