rs5743572

Positions:

• chr4-38803770-C-T

Variant summary

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

The ENST00000308979.7(TLR1):​c.-160+536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,190 control chromosomes in the GnomAD database, including 320 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 0.056 (320 hom., cov: 32)
• Consequence: TLR1 ENST00000308979.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-160+536G>A		intron_variant		ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-160+536G>A		intron_variant		1	NM_003263.4	ENSP00000354932	P1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8502 AN: 152074 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0559 AC: 8509 AN: 152190 Hom.: 320 Cov.: 32 AF XY: 0.0553 AC XY: 4114 AN XY: 74426

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0427 Hom.: 111

Bravo AF: 0.0587

Asia WGS AF: 0.0890 AC: 309 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.40

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: rs5743572; hg19: chr4-38805391;