rs5743553

Variant names:

• chr4-38805568-A-T
• rs5743553
• ENST00000508364.1:c.-524T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508364.1(TLR1):​c.-524T>A 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 0.0521 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 3 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508364.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000508364.1	TSL:4	c.-524T>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000424894.1	D6RF68
	TLR1	ENST00000508364.1	TSL:4	c.-524T>A		5_prime_UTR	Exon 1 of 2	ENSP00000424894.1	D6RF68
	TLR1	ENST00000506146.5	TSL:4	c.-352-375T>A		intron	N/A	ENSP00000423725.1	D6RCE8

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

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: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.140 AC: 5797 AN: 41472

American (AMR) AF: 0.0264 AC: 404 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.0715 AC: 371 AN: 5186

South Asian (SAS) AF: 0.0901 AC: 434 AN: 4818

European-Finnish (FIN) AF: 0.00885 AC: 94 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00880 AC: 599 AN: 68030

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		0.29
PromoterAI		-0.039	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5743553; hg19: chr4-38807189;