4-38830547-T-C

Position:

• chr4-38830547-T-C

Variant summary

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

The NM_006068.5(TLR6):​c.-64-1010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,798 control chromosomes in the GnomAD database, including 13,674 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 0.40 (13674 hom., cov: 31)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-1010A>G		intron_variant		ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.-64-1010A>G		intron_variant		1	NM_006068.5	ENSP00000424718	P1
TLR6	ENST00000381950.2	c.-64-1010A>G		intron_variant				ENSP00000371376	P1
TLR1	ENST00000506146.5	c.-352-25354A>G		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61005 AN: 151680 Hom.: 13656 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.402 AC: 61072 AN: 151798 Hom.: 13674 Cov.: 31 AF XY: 0.402 AC XY: 29854 AN XY: 74186

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.362

Alfa AF: 0.388 Hom.: 1529

Bravo AF: 0.403

Asia WGS AF: 0.428 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.58

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: rs5743802; hg19: chr4-38832168;