rs2192617

chr1-223138108-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.-438-845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 150,804 control chromosomes in the GnomAD database, including 1,369 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 0.12 (1369 hom., cov: 26)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR5	NM_003268.6	c.-438-845C>T		intron_variant		ENST00000642603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR5	ENST00000642603.2	c.-438-845C>T		intron_variant			NM_003268.6	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17890 AN: 150684 Hom.: 1368 Cov.: 26

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.119 AC: 17898 AN: 150804 Hom.: 1369 Cov.: 26 AF XY: 0.121 AC XY: 8917 AN XY: 73580

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.121

Alfa AF: 0.118 Hom.: 172

Bravo AF: 0.119

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2192617; hg19: chr1-223311450; COSMIC: COSV60558375; COSMIC: COSV60558375;