NM_003263.4:c.-175C>G

Variant names:

• chr4-38804321-G-C
• rs5743566
• NM_003263.4:c.-175C>G

Variant summary

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

The NM_003263.4(TLR1):​c.-175C>G 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 0.146 in 152,362 control chromosomes in the GnomAD database, including 2,249 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 0.15 (2244 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5 hom.)
• Consequence: TLR1 NM_003263.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 22 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 = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003263.4. 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
	TLR1	NM_003263.4	MANE Select	c.-175C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_003254.2
	TLR1	NM_003263.4	MANE Select	c.-175C>G		5_prime_UTR	Exon 2 of 4	NP_003254.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-175C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000354932.2	Q15399
	TLR1	ENST00000502213.7	TSL:1	c.-175C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000421259.1	Q15399
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-175C>G		5_prime_UTR	Exon 2 of 4	ENSP00000354932.2	Q15399

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22247 AN: 152122 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.172 AC: 21 AN: 122 Hom.: 5 Cov.: 0 AF XY: 0.162 AC XY: 11 AN XY: 68

African (AFR) AF: 0.00 AC: 0 AN: 2

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: 0.242 AC: 16 AN: 66

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0962 AC: 5 AN: 52

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22240 AN: 152240 Hom.: 2244 Cov.: 32 AF XY: 0.145 AC XY: 10784 AN XY: 74428

African (AFR) AF: 0.0343 AC: 1426 AN: 41568

American (AMR) AF: 0.175 AC: 2670 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5174

South Asian (SAS) AF: 0.195 AC: 941 AN: 4816

European-Finnish (FIN) AF: 0.0834 AC: 884 AN: 10600

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12390 AN: 67998

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.152 Hom.: 285

Bravo AF: 0.152

Asia WGS AF: 0.230 AC: 797 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.54
PhyloP100		-0.48
PromoterAI		0.0098	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.38		Position offset: -15

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

Other links and lift over

dbSNP: rs5743566; hg19: chr4-38805942;