chr1-223143343-C-A

Variant names:

• chr1-223143343-C-A
• rs1773766
• NM_003268.6:c.-702G>T

Variant summary

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

The NM_003268.6(TLR5):​c.-702G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 152,412 control chromosomes in the GnomAD database, including 815 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 0.080 (815 hom., cov: 33)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: TLR5 NM_003268.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

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]

LOC124904522 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-702G>T		upstream_gene_variant		ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-702G>T		upstream_gene_variant			NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12073 AN: 152168 Hom.: 809 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0578

GnomAD4 exome AF: 0.0159 AC: 2 AN: 126 Hom.: 0 AF XY: 0.0204 AC XY: 2 AN XY: 98

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0795 AC: 12111 AN: 152286 Hom.: 815 Cov.: 33 AF XY: 0.0787 AC XY: 5862 AN XY: 74466

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0938

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0409

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0169 Hom.: 7

Bravo AF: 0.0847

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
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: rs1773766; hg19: chr1-223316685;