4-38827028-A-G

Variant names:

• chr4-38827028-A-G
• rs5743823
• NM_006068.5:c.*55T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006068.5(TLR6):​c.*55T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,356,248 control chromosomes in the GnomAD database, including 79 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 0.0077 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (73 hom.)
• Consequence: TLR6 NM_006068.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• 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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00771 (1174/152350) while in subpopulation SAS AF = 0.0381 (184/4826). AF 95% confidence interval is 0.0336. There are 6 homozygotes in GnomAd4. There are 602 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006068.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	NM_006068.5	MANE Select	c.*55T>C		3_prime_UTR	Exon 2 of 2	NP_006059.2
	TLR6	NM_001394553.1		c.*55T>C		3_prime_UTR	Exon 2 of 2	NP_001381482.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.*55T>C		3_prime_UTR	Exon 2 of 2	ENSP00000424718.2
	TLR6	ENST00000381950.2	TSL:6	c.*55T>C		3_prime_UTR	Exon 3 of 3	ENSP00000371376.1
	TLR1	ENST00000506146.5	TSL:4	c.-352-21835T>C		intron	N/A	ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1174 AN: 152232 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.00764

GnomAD4 exome AF: 0.00637 AC: 7672 AN: 1203898 Hom.: 73 Cov.: 17 AF XY: 0.00714 AC XY: 4241 AN XY: 593876

African (AFR) AF: 0.0108 AC: 288 AN: 26698

American (AMR) AF: 0.00630 AC: 154 AN: 24432

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 69 AN: 19566

East Asian (EAS) AF: 0.0151 AC: 531 AN: 35104

South Asian (SAS) AF: 0.0343 AC: 2150 AN: 62712

European-Finnish (FIN) AF: 0.00125 AC: 50 AN: 40020

Middle Eastern (MID) AF: 0.0247 AC: 88 AN: 3556

European-Non Finnish (NFE) AF: 0.00420 AC: 3953 AN: 940872

Other (OTH) AF: 0.00764 AC: 389 AN: 50938

GnomAD4 genome AF: 0.00771 AC: 1174 AN: 152350 Hom.: 6 Cov.: 33 AF XY: 0.00808 AC XY: 602 AN XY: 74498

African (AFR) AF: 0.0105 AC: 435 AN: 41590

American (AMR) AF: 0.00974 AC: 149 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00867 AC: 45 AN: 5190

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4826

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00462 AC: 314 AN: 68026

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00608 Hom.: 2

Bravo AF: 0.00797

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism

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: rs5743823; hg19: chr4-38828649;