rs851178

Variant names:

• chr1-223133089-G-A
• rs851178
• NM_003268.6:c.-169-450C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-223133089-G-A
• chr1-223133089-G-C
• chr1-223133089-G-T

Variant summary

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

The NM_003268.6(TLR5):​c.-169-450C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,080 control chromosomes in the GnomAD database, including 32,545 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 0.65 (32545 hom., cov: 32)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 10 publications found

Genes affected

TLR5 (HGNC:11851): (toll like receptor 5) This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003268.6. 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
	TLR5	NM_003268.6	MANE Select	c.-169-450C>T		intron	N/A	NP_003259.2
	TLR5	NM_001437539.1		c.-169-450C>T		intron	N/A	NP_001424468.1
	TLR5	NM_001437624.1		c.-169-450C>T		intron	N/A	NP_001424553.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	ENST00000642603.2	MANE Select	c.-169-450C>T		intron	N/A	ENSP00000496355.1
	TLR5	ENST00000407096.7	TSL:3	c.-169-450C>T		intron	N/A	ENSP00000385458.3
	TLR5	ENST00000484766.2	TSL:3	c.-169-450C>T		intron	N/A	ENSP00000519510.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98057 AN: 151962 Hom.: 32518 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.645 AC: 98132 AN: 152080 Hom.: 32545 Cov.: 32 AF XY: 0.643 AC XY: 47810 AN XY: 74350

African (AFR) AF: 0.792 AC: 32882 AN: 41492

American (AMR) AF: 0.671 AC: 10246 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4104 AN: 5170

South Asian (SAS) AF: 0.574 AC: 2765 AN: 4820

European-Finnish (FIN) AF: 0.506 AC: 5340 AN: 10554

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38695 AN: 67982

Other (OTH) AF: 0.653 AC: 1378 AN: 2110

Alfa AF: 0.592 Hom.: 78087

Bravo AF: 0.668

Asia WGS AF: 0.692 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.78
PhyloP100		-0.51
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: rs851178; hg19: chr1-223306431; COSMIC: COSV60559308; COSMIC: COSV60559308;