rs5743553

Positions:

• chr4-38805568-A-T

Variant summary

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

The ENST00000508364.1(TLR1):​c.-524T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,212 control chromosomes in the GnomAD database, including 484 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 0.052 (484 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR1 ENST00000508364.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	XM_005262662.6	c.-727T>A		5_prime_UTR_variant	1/5		XP_005262719.1
TLR1	XM_011513742.4	c.-650T>A		5_prime_UTR_variant	1/4		XP_011512044.1
TLR1	XM_011513745.4	c.-558T>A		5_prime_UTR_variant	1/3		XP_011512047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000508364.1	c.-524T>A		5_prime_UTR_variant	1/2	4		ENSP00000424894
TLR1	ENST00000506146.5	c.-352-375T>A		intron_variant		4		ENSP00000423725
TLR1	ENST00000508535.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7903 AN: 152094 Hom.: 478 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00880

Gnomad OTH AF: 0.0541

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0521 AC: 7936 AN: 152212 Hom.: 484 Cov.: 32 AF XY: 0.0522 AC XY: 3884 AN XY: 74436

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.0715

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.00880

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0330 Hom.: 25

Bravo AF: 0.0564

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743553; hg19: chr4-38807189;