rs5743596

Positions:

• chr4-38800907-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003263.4(TLR1):​c.-118C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,610 control chromosomes in the GnomAD database, including 1,623 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 0.12 (1621 hom., cov: 32)
  • Exomes 𝑓: 0.083 (2 hom.)
• Consequence: TLR1 NM_003263.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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]

TLR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-118C>T		5_prime_UTR_premature_start_codon_gain_variant	3/4	ENST00000308979.7	NP_003254.2
TLR1	NM_003263.4	c.-118C>T		5_prime_UTR_variant	3/4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-118C>T		5_prime_UTR_premature_start_codon_gain_variant	3/4	1	NM_003263.4	ENSP00000354932.2
TLR1	ENST00000308979.7	c.-118C>T		5_prime_UTR_variant	3/4	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18973 AN: 152058 Hom.: 1620 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.0829 AC: 36 AN: 434 Hom.: 2 Cov.: 0 AF XY: 0.0992 AC XY: 26 AN XY: 262

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.125 AC: 18968 AN: 152176 Hom.: 1621 Cov.: 32 AF XY: 0.122 AC XY: 9088 AN XY: 74404

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.176

Alfa AF: 0.173 Hom.: 2762

Bravo AF: 0.129

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.33		Position offset: 41

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743596; hg19: chr4-38802528; COSMIC: COSV58304325;