rs4833103

Variant names:

• chr4-38813881-A-C
• rs4833103
• ENST00000506146.5:c.-352-8688T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000506146.5(TLR1):​c.-352-8688T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,204 control chromosomes in the GnomAD database, including 36,512 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 (36512 hom., cov: 33)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-8688T>G		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 99077 AN: 152086 Hom.: 36444 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.652 AC: 99206 AN: 152204 Hom.: 36512 Cov.: 33 AF XY: 0.653 AC XY: 48555 AN XY: 74402

African (AFR) AF: 0.915 AC: 38005 AN: 41544

American (AMR) AF: 0.758 AC: 11583 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2446 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5190 AN: 5194

South Asian (SAS) AF: 0.975 AC: 4694 AN: 4814

European-Finnish (FIN) AF: 0.261 AC: 2760 AN: 10576

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32317 AN: 68006

Other (OTH) AF: 0.720 AC: 1520 AN: 2112

Alfa AF: 0.572 Hom.: 63432

Bravo AF: 0.698

Asia WGS AF: 0.965 AC: 3355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.85
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs4833103; hg19: chr4-38815502;