chr4-38806033-T-C

Variant names:

• chr4-38806033-T-C
• rs5743551
• ENST00000506146.5:c.-352-840A>G

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-840A>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
• Publications: 77 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506146.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000506146.5	TSL:4	c.-352-840A>G		intron	N/A	ENSP00000423725.1	D6RCE8

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

African (AFR) AF: 0.795 AC: 32938 AN: 41408

American (AMR) AF: 0.505 AC: 7700 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3073 AN: 5160

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4820

European-Finnish (FIN) AF: 0.118 AC: 1253 AN: 10576

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16244 AN: 67944

Other (OTH) AF: 0.490 AC: 1031 AN: 2104

Alfa AF: 0.304 Hom.: 14346

Bravo AF: 0.482

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		-1.9
PromoterAI		-0.022	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5743551; hg19: chr4-38807654;