rs5743599

chr4-38800543-G-Achr4-38800543-G-T

Variant summary

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

The NM_003263.4(TLR1):c.-68+314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,010 control chromosomes in the GnomAD database, including 985 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 0.072 (985 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4	c.-68+314C>T		intron_variant		ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000308979.7	c.-68+314C>T		intron_variant		1	NM_003263.4	P1

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10876 AN: 151888 Hom.: 981 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.00513

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.0656

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 106 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0717 AC: 10899 AN: 152010 Hom.: 985 Cov.: 32 AF XY: 0.0764 AC XY: 5680 AN XY: 74316

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.00513

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0441 Hom.: 258

Bravo AF: 0.0885

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.52
Dann	Benign	0.77

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: rs5743599; hg19: chr4-38802164;