4-38825793-T-C

Variant names:

• chr4-38825793-T-C
• rs5743831
• NM_006068.5:c.*1290A>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.*1290A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,248 control chromosomes in the GnomAD database, including 1,421 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 0.094 (1421 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.27 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.*1290A>G		3_prime_UTR	Exon 2 of 2	NP_006059.2
	TLR6	NM_001394553.1		c.*1290A>G		3_prime_UTR	Exon 2 of 2	NP_001381482.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.*1290A>G		3_prime_UTR	Exon 2 of 2	ENSP00000424718.2
	TLR6	ENST00000966018.1		c.*1290A>G		3_prime_UTR	Exon 2 of 2	ENSP00000636077.1
	TLR1	ENST00000506146.5	TSL:4	c.-352-20600A>G		intron	N/A	ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14286 AN: 152108 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0625 AC: 1 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0939 AC: 14293 AN: 152226 Hom.: 1421 Cov.: 32 AF XY: 0.0978 AC XY: 7278 AN XY: 74416

African (AFR) AF: 0.214 AC: 8885 AN: 41530

American (AMR) AF: 0.146 AC: 2236 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1455 AN: 5162

South Asian (SAS) AF: 0.127 AC: 615 AN: 4828

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 709 AN: 68022

Other (OTH) AF: 0.0833 AC: 176 AN: 2114

Alfa AF: 0.0356 Hom.: 719

Bravo AF: 0.108

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.81
PhyloP100		0.50
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: rs5743831; hg19: chr4-38827414;