chr1-223132068-A-C

Variant names:

• chr1-223132068-A-C
• rs851186
• NM_003268.6:c.-5+407T>G

Variant summary

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

The NM_003268.6(TLR5):​c.-5+407T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,840 control chromosomes in the GnomAD database, including 30,896 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 0.63 (30896 hom., cov: 30)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

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.-5+407T>G		intron	N/A	NP_003259.2
	TLR5	NM_001437539.1		c.-5+407T>G		intron	N/A	NP_001424468.1	A0A2R8Y7Z4
	TLR5	NM_001437624.1		c.-5+407T>G		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.-5+407T>G		intron	N/A	ENSP00000496355.1	A0A2R8Y7Z4
	TLR5	ENST00000407096.7	TSL:3	c.-5+407T>G		intron	N/A	ENSP00000385458.3	B1AZ06
	TLR5	ENST00000484766.2	TSL:3	c.-5+407T>G		intron	N/A	ENSP00000519510.1	O60602

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95831 AN: 151718 Hom.: 30874 Cov.: 30

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.632 AC: 95904 AN: 151840 Hom.: 30896 Cov.: 30 AF XY: 0.629 AC XY: 46694 AN XY: 74200

African (AFR) AF: 0.746 AC: 30891 AN: 41432

American (AMR) AF: 0.664 AC: 10137 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3464

East Asian (EAS) AF: 0.794 AC: 4076 AN: 5134

South Asian (SAS) AF: 0.574 AC: 2745 AN: 4786

European-Finnish (FIN) AF: 0.507 AC: 5331 AN: 10518

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38689 AN: 67934

Other (OTH) AF: 0.640 AC: 1347 AN: 2104

Alfa AF: 0.589 Hom.: 3323

Bravo AF: 0.651

Asia WGS AF: 0.693 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.92
PhyloP100		0.70
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: rs851186; hg19: chr1-223305410; COSMIC: COSV60558343; COSMIC: COSV60558343;