1-223116005-T-C

Position:

• chr1-223116005-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.-4-2970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,110 control chromosomes in the GnomAD database, including 36,836 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 0.68 (36836 hom., cov: 32)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR5	NM_003268.6	c.-4-2970A>G		intron_variant		ENST00000642603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR5	ENST00000642603.2	c.-4-2970A>G		intron_variant			NM_003268.6	P1
TLR5	ENST00000407096.6	c.-4-2970A>G		intron_variant		3
TLR5	ENST00000540964.5	c.-4-2970A>G		intron_variant		5		P1
TLR5	ENST00000645434.1	c.-4-2970A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.684 AC: 104032 AN: 151992 Hom.: 36807 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.684 AC: 104115 AN: 152110 Hom.: 36836 Cov.: 32 AF XY: 0.680 AC XY: 50528 AN XY: 74344

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.666

Alfa AF: 0.579 Hom.: 4603

Bravo AF: 0.708

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.27

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: rs851139; hg19: chr1-223289347;