rs2381290

Variant names:

• chr4-38825193-T-A
• rs2381290
• NM_006068.5:c.*1890A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-38825193-T-A
• chr4-38825193-T-C
• chr4-38825193-T-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.*1890A>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 0.373 in 152,102 control chromosomes in the GnomAD database, including 11,780 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 0.37 (11780 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5	c.*1890A>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.*1890A>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2
TLR1	ENST00000506146.5	c.-352-20000A>T		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56732 AN: 151968 Hom.: 11770 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.250 AC: 4 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

African (AFR) AF: 0.00 AC: 0 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) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.373 AC: 56775 AN: 152086 Hom.: 11780 Cov.: 32 AF XY: 0.369 AC XY: 27418 AN XY: 74332

African (AFR) AF: 0.200 AC: 8318 AN: 41514

American (AMR) AF: 0.303 AC: 4636 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1929 AN: 5168

South Asian (SAS) AF: 0.367 AC: 1772 AN: 4824

European-Finnish (FIN) AF: 0.443 AC: 4673 AN: 10538

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32225 AN: 67974

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.326 Hom.: 1040

Bravo AF: 0.357

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		0.81
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: rs2381290; hg19: chr4-38826814;