NM_003268.6:c.-438-1002G>C

Variant names:

• chr1-223138265-C-G
• rs1640827
• NM_003268.6:c.-438-1002G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003268.6(TLR5):​c.-438-1002G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 11 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]

TLR5 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus, susceptibility to, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003268.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	NM_003268.6	MANE Select	c.-438-1002G>C		intron	N/A	NP_003259.2
	TLR5	NM_001437539.1		c.-532-1002G>C		intron	N/A	NP_001424468.1	A0A2R8Y7Z4
	TLR5	NM_001437624.1		c.-352-3401G>C		intron	N/A	NP_001424553.1	A0A2R8Y7Z4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR5	ENST00000642603.2	MANE Select	c.-438-1002G>C		intron	N/A	ENSP00000496355.1	A0A2R8Y7Z4
	TLR5	ENST00000407096.7	TSL:3	c.-352-3401G>C		intron	N/A	ENSP00000385458.3	B1AZ06
	TLR5	ENST00000484766.2	TSL:3	c.-532-1002G>C		intron	N/A	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 33517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.59
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1640827; hg19: chr1-223311607;