chr1-223138265-C-T

Position:

• chr1-223138265-C-T

Variant summary

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

The NM_003268.6(TLR5):​c.-438-1002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,642 control chromosomes in the GnomAD database, including 35,328 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 0.66 (35328 hom., cov: 30)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR5	NM_003268.6	c.-438-1002G>A		intron_variant		ENST00000642603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR5	ENST00000642603.2	c.-438-1002G>A		intron_variant			NM_003268.6	P1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100628 AN: 151522 Hom.: 35279 Cov.: 30

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.664 AC: 100727 AN: 151642 Hom.: 35328 Cov.: 30 AF XY: 0.662 AC XY: 49056 AN XY: 74072

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.644

Alfa AF: 0.579 Hom.: 24187

Bravo AF: 0.689

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1640827; hg19: chr1-223311607; COSMIC: COSV60558378; COSMIC: COSV60558378;