rs17616434

Positions:

• chr4-38811255-T-C

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-6062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,108 control chromosomes in the GnomAD database, including 19,448 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 0.44 (19448 hom., cov: 32)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-6062A>G		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66551 AN: 151990 Hom.: 19400 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.438 AC: 66661 AN: 152108 Hom.: 19448 Cov.: 32 AF XY: 0.437 AC XY: 32514 AN XY: 74396

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.492

Alfa AF: 0.328 Hom.: 10286

Bravo AF: 0.484

Asia WGS AF: 0.548 AC: 1904 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	0.87
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17616434; hg19: chr4-38812876;