chr1-223110509-T-C

Position:

• chr1-223110509-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003268.6(TLR5):​c.2523A>G​(p.Lys841=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,614,048 control chromosomes in the GnomAD database, including 7,323 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 0.069 (451 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6872 hom.)
• Consequence: TLR5 NM_003268.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.457 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.2523A>G	p.Lys841=	synonymous_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.2523A>G	p.Lys841=	synonymous_variant	6/6		NM_003268.6	ENSP00000496355	P1
TLR5	ENST00000540964.5	c.2523A>G	p.Lys841=	synonymous_variant	4/4	5		ENSP00000440643	P1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10500 AN: 152180 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0927

GnomAD3 exomes AF: 0.0744 AC: 18687 AN: 251192 Hom.: 911 AF XY: 0.0753 AC XY: 10228 AN XY: 135754

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.0522

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.0394

Gnomad FIN exome AF: 0.0802

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0891

GnomAD4 exome AF: 0.0922 AC: 134743 AN: 1461750 Hom.: 6872 Cov.: 33 AF XY: 0.0914 AC XY: 66458 AN XY: 727180

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.0406

Gnomad4 FIN exome AF: 0.0790

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0856

GnomAD4 genome AF: 0.0689 AC: 10496 AN: 152298 Hom.: 451 Cov.: 32 AF XY: 0.0658 AC XY: 4900 AN XY: 74454

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0934 Hom.: 394

Bravo AF: 0.0675

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.54

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: rs1053954; hg19: chr1-223283851;