4-38830874-C-T

Variant names:

• chr4-38830874-C-T
• rs5743795
• NM_006068.5:c.-64-1337G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006068.5(TLR6):​c.-64-1337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,078 control chromosomes in the GnomAD database, including 2,307 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 0.15 (2307 hom., cov: 32)
• Consequence: TLR6 NM_006068.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 24 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.-64-1337G>A		intron_variant	Intron 1 of 1	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.-64-1337G>A		intron_variant	Intron 1 of 1	1	NM_006068.5	ENSP00000424718.2
TLR6	ENST00000381950.2	c.-64-1337G>A		intron_variant	Intron 2 of 2	6		ENSP00000371376.1
TLR1	ENST00000506146.5	c.-352-25681G>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22947 AN: 151960 Hom.: 2308 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.151 AC: 22943 AN: 152078 Hom.: 2307 Cov.: 32 AF XY: 0.149 AC XY: 11092 AN XY: 74336

African (AFR) AF: 0.0390 AC: 1618 AN: 41522

American (AMR) AF: 0.183 AC: 2794 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1160 AN: 3464

East Asian (EAS) AF: 0.346 AC: 1792 AN: 5176

South Asian (SAS) AF: 0.218 AC: 1054 AN: 4828

European-Finnish (FIN) AF: 0.0817 AC: 863 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12836 AN: 67960

Other (OTH) AF: 0.216 AC: 455 AN: 2108

Alfa AF: 0.0768 Hom.: 117

Bravo AF: 0.156

Asia WGS AF: 0.222 AC: 770 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.27
PhyloP100		-1.2
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: rs5743795; hg19: chr4-38832495;