rs2890664

Variant names:

• chr4-38825357-C-A
• rs2890664
• NM_006068.5:c.*1726G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-38825357-C-A
• chr4-38825357-C-G
• chr4-38825357-C-T

Variant summary

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

The NM_006068.5(TLR6):​c.*1726G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,044 control chromosomes in the GnomAD database, including 14,425 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 0.42 (14419 hom., cov: 32)
  • Exomes 𝑓: 0.53 (6 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.*1726G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6	c.*1726G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR1	ENST00000506146.5	c.-352-20164G>T		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64124 AN: 151888 Hom.: 14402 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.526 AC: 20 AN: 38 Hom.: 6 Cov.: 0 AF XY: 0.458 AC XY: 11 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

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: 0.529 AC: 18 AN: 34

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.422 AC: 64185 AN: 152006 Hom.: 14419 Cov.: 32 AF XY: 0.418 AC XY: 31048 AN XY: 74266

African (AFR) AF: 0.290 AC: 12014 AN: 41466

American (AMR) AF: 0.336 AC: 5130 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3464

East Asian (EAS) AF: 0.445 AC: 2290 AN: 5148

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4820

European-Finnish (FIN) AF: 0.487 AC: 5134 AN: 10542

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34191 AN: 67968

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.352 Hom.: 1172

Bravo AF: 0.406

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.37
PhyloP100		-0.86
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: rs2890664; hg19: chr4-38826978;