NM_003268.6:c.-353+472C>T

Variant names:

• chr1-223136706-G-A
• rs2241096
• NM_003268.6:c.-353+472C>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.-353+472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,254 control chromosomes in the GnomAD database, including 811 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 0.084 (811 hom., cov: 32)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-353+472C>T		intron_variant	Intron 3 of 5	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-353+472C>T		intron_variant	Intron 3 of 5		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12872 AN: 152136 Hom.: 811 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0845 AC: 12865 AN: 152254 Hom.: 811 Cov.: 32 AF XY: 0.0863 AC XY: 6422 AN XY: 74434

African (AFR) AF: 0.0215 AC: 893 AN: 41568

American (AMR) AF: 0.0696 AC: 1064 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5168

South Asian (SAS) AF: 0.179 AC: 863 AN: 4826

European-Finnish (FIN) AF: 0.0915 AC: 970 AN: 10604

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6880 AN: 68002

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.0972 Hom.: 1361

Bravo AF: 0.0806

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.22
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241096; hg19: chr1-223310048;