rs5743596

Variant names:

• chr4-38800907-G-A
• rs5743596
• NM_003263.4:c.-118C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000308979.7(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 ENST00000308979.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 35 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]

ENSG00000306984 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000308979.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	NM_003263.4	MANE Select	c.-118C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_003254.2
	TLR1	NM_003263.4	MANE Select	c.-118C>T		5_prime_UTR	Exon 3 of 4	NP_003254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-118C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.-118C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000421259.1
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-118C>T		5_prime_UTR	Exon 3 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0822 AC: 35 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.0290 AC: 1205 AN: 41528

American (AMR) AF: 0.145 AC: 2211 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1477 AN: 5176

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.0659 AC: 698 AN: 10594

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10850 AN: 67982

Other (OTH) AF: 0.176 AC: 372 AN: 2116

Alfa AF: 0.163 Hom.: 4043

Bravo AF: 0.129

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.11
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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