rs851138

Variant names:

• chr1-223116031-C-A
• rs851138
• NM_003268.6:c.-4-2996G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-223116031-C-A
• chr1-223116031-C-G
• chr1-223116031-C-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.-4-2996G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,150 control chromosomes in the GnomAD database, including 34,323 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 0.66 (34323 hom., cov: 33)
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-4-2996G>T		intron_variant	Intron 5 of 5	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-4-2996G>T		intron_variant	Intron 5 of 5		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100278 AN: 152032 Hom.: 34290 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.660 AC: 100367 AN: 152150 Hom.: 34323 Cov.: 33 AF XY: 0.656 AC XY: 48839 AN XY: 74394

African (AFR) AF: 0.843 AC: 34995 AN: 41536

American (AMR) AF: 0.676 AC: 10337 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2082 AN: 3466

East Asian (EAS) AF: 0.790 AC: 4085 AN: 5168

South Asian (SAS) AF: 0.572 AC: 2749 AN: 4808

European-Finnish (FIN) AF: 0.506 AC: 5358 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38738 AN: 67988

Other (OTH) AF: 0.658 AC: 1385 AN: 2106

Alfa AF: 0.438 Hom.: 1046

Bravo AF: 0.685

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		-0.45
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: rs851138; hg19: chr1-223289373;