rs1053954

Variant names:

• chr1-223110509-T-C
• rs1053954
• NM_003268.6:c.2523A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-223110509-T-C
• chr1-223110509-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003268.6(TLR5):​c.2523A>G​(p.Lys841Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,614,048 control chromosomes in the GnomAD database, including 7,323 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 0.069 (451 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6872 hom.)
• Consequence: TLR5 NM_003268.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457
• Publications: 18 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]

ENSG00000299361 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.457 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.2523A>G	p.Lys841Lys	synonymous_variant	Exon 6 of 6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.2523A>G	p.Lys841Lys	synonymous_variant	Exon 6 of 6		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10500 AN: 152180 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0927

GnomAD2 exomes AF: 0.0744 AC: 18687 AN: 251192 AF XY: 0.0753

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.0522

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0802

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0891

GnomAD4 exome AF: 0.0922 AC: 134743 AN: 1461750 Hom.: 6872 Cov.: 33 AF XY: 0.0914 AC XY: 66458 AN XY: 727180

African (AFR) AF: 0.0150 AC: 502 AN: 33468

American (AMR) AF: 0.0543 AC: 2425 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3141 AN: 26132

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39686

South Asian (SAS) AF: 0.0406 AC: 3503 AN: 86254

European-Finnish (FIN) AF: 0.0790 AC: 4221 AN: 53412

Middle Eastern (MID) AF: 0.0955 AC: 551 AN: 5768

European-Non Finnish (NFE) AF: 0.104 AC: 115207 AN: 1111940

Other (OTH) AF: 0.0856 AC: 5172 AN: 60390

GnomAD4 genome AF: 0.0689 AC: 10496 AN: 152298 Hom.: 451 Cov.: 32 AF XY: 0.0658 AC XY: 4900 AN XY: 74454

African (AFR) AF: 0.0189 AC: 786 AN: 41570

American (AMR) AF: 0.0722 AC: 1105 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4826

European-Finnish (FIN) AF: 0.0717 AC: 760 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6982 AN: 68018

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0934 Hom.: 394

Bravo AF: 0.0675

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		0.46
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: rs1053954; hg19: chr1-223283851;