1-223109474-G-A

Position:

• chr1-223109474-G-A

Variant summary

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

The NM_003268.6(TLR5):​c.*981C>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 0.329 in 151,834 control chromosomes in the GnomAD database, including 9,687 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 0.33 (9687 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: TLR5 NM_003268.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.*981C>T		3_prime_UTR_variant	6/6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.*981C>T		3_prime_UTR_variant	6/6		NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000540964.5	c.*981C>T		3_prime_UTR_variant	4/4	5		ENSP00000440643	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49850 AN: 151714 Hom.: 9682 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.329 AC: 49878 AN: 151832 Hom.: 9687 Cov.: 32 AF XY: 0.331 AC XY: 24562 AN XY: 74142

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.334

Alfa AF: 0.386 Hom.: 1508

Bravo AF: 0.303

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs45508499; hg19: chr1-223282816;