chr4-38806033-T-C

Position:

• chr4-38806033-T-C

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-840A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,948 control chromosomes in the GnomAD database, including 19,313 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 (19313 hom., cov: 31)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.38806033T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-840A>G		intron_variant		4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66289 AN: 151830 Hom.: 19263 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.437 AC: 66401 AN: 151948 Hom.: 19313 Cov.: 31 AF XY: 0.436 AC XY: 32388 AN XY: 74266

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.490

Alfa AF: 0.298 Hom.: 8646

Bravo AF: 0.482

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743551; hg19: chr4-38807654;