rs5743594

chr4-38801130-G-Achr4-38801130-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003263.4(TLR1):c.-159-182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,238 control chromosomes in the GnomAD database, including 1,487 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 (1487 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4	c.-159-182C>T		intron_variant		ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000308979.7	c.-159-182C>T		intron_variant		1	NM_003263.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17847 AN: 152118 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.117 AC: 17841 AN: 152238 Hom.: 1487 Cov.: 32 AF XY: 0.110 AC XY: 8193 AN XY: 74440

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.105

Alfa AF: 0.147 Hom.: 965

Bravo AF: 0.113

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743594; hg19: chr4-38802751;