1-223138521-T-C

Position:

• chr1-223138521-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003268.6(TLR5):​c.-438-1258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,846 control chromosomes in the GnomAD database, including 28,383 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 0.60 (28383 hom., cov: 31)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

TLR5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-438-1258A>G		intron_variant		ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-438-1258A>G		intron_variant			NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91228 AN: 151728 Hom.: 28361 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.601 AC: 91295 AN: 151846 Hom.: 28383 Cov.: 31 AF XY: 0.599 AC XY: 44471 AN XY: 74182

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.600

Alfa AF: 0.573 Hom.: 5421

Bravo AF: 0.623

Asia WGS AF: 0.684 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2353476; hg19: chr1-223311863;