chr1-223140596-G-A

Variant names:

• chr1-223140596-G-A
• rs5744113
• NM_003268.6:c.-439+1052C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003268.6(TLR5):​c.-439+1052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,018 control chromosomes in the GnomAD database, including 25,454 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 0.57 (25454 hom., cov: 28)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-439+1052C>T		intron_variant	Intron 2 of 5	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-439+1052C>T		intron_variant	Intron 2 of 5		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86381 AN: 150908 Hom.: 25445 Cov.: 28

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.572 AC: 86430 AN: 151018 Hom.: 25454 Cov.: 28 AF XY: 0.572 AC XY: 42108 AN XY: 73634

African (AFR) AF: 0.677 AC: 27792 AN: 41022

American (AMR) AF: 0.614 AC: 9339 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1891 AN: 3464

East Asian (EAS) AF: 0.754 AC: 3841 AN: 5092

South Asian (SAS) AF: 0.567 AC: 2717 AN: 4796

European-Finnish (FIN) AF: 0.466 AC: 4781 AN: 10258

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34279 AN: 67864

Other (OTH) AF: 0.576 AC: 1210 AN: 2100

Alfa AF: 0.538 Hom.: 3297

Bravo AF: 0.593

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5744113; hg19: chr1-223313938; COSMIC: COSV64827097; COSMIC: COSV64827097;