1-223132439-G-C

Position:

• chr1-223132439-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003268.6(TLR5):​c.-5+36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,602 control chromosomes in the GnomAD database, including 33,152 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 0.65 (33152 hom., cov: 32)
  • Exomes 𝑓: 0.54 (19 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR5 NM_003268.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR5	NM_003268.6	c.-5+36C>G		intron_variant		ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.-5+36C>G		intron_variant			NM_003268.6	ENSP00000496355	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98626 AN: 151482 Hom.: 33116 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.657

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.536 AC: 74 AN: 138 Hom.: 19 Cov.: 0 AF XY: 0.539 AC XY: 41 AN XY: 76

Gnomad4 EAS exome AF: 0.536

GnomAD4 genome AF: 0.651 AC: 98718 AN: 151602 Hom.: 33152 Cov.: 32 AF XY: 0.649 AC XY: 48053 AN XY: 74092

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.656

Alfa AF: 0.592 Hom.: 3228

Bravo AF: 0.675

Asia WGS AF: 0.699 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs851183; hg19: chr1-223305781; COSMIC: COSV60558362; COSMIC: COSV60558362;