4-38855458-T-G

Position:

• chr4-38855458-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006068.5(TLR6):​c.-65+1303A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 5,004 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 (5004 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-65+1303A>C		intron_variant		ENST00000508254.6	NP_006059.2
TLR6	NM_001394553.1	c.-65+2230A>C		intron_variant			NP_001381482.1
TLR6	XM_047449496.1	c.-218+1303A>C		intron_variant			XP_047305452.1
TLR6	XM_047449498.1	c.-65+12468A>C		intron_variant			XP_047305454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.-65+1303A>C		intron_variant		1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-218+1303A>C		intron_variant		6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-353+1303A>C		intron_variant		4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36860 AN: 151984 Hom.: 4991 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.243 AC: 36891 AN: 152102 Hom.: 5004 Cov.: 32 AF XY: 0.238 AC XY: 17675 AN XY: 74338

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0639

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.196

Alfa AF: 0.291 Hom.: 871

Bravo AF: 0.226

Asia WGS AF: 0.116 AC: 401 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2087465; hg19: chr4-38857079;