rs4543123

Positions:

• chr4-38790903-A-G

Variant summary

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

The ENST00000510552.1(TLR1):​n.426T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,148 control chromosomes in the GnomAD database, including 9,021 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 0.32 (9021 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TLR1 ENST00000510552.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	XR_007057953.1	n.2987T>C		non_coding_transcript_exon_variant	4/4
TLR1	XR_007057954.1	n.2895T>C		non_coding_transcript_exon_variant	3/3
TLR1	XR_925165.3	n.3064T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000505744.5	n.564T>C		non_coding_transcript_exon_variant	4/4	3
TLR1	ENST00000510552.1	n.426T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47933 AN: 152026 Hom.: 8993 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.316 AC: 48011 AN: 152144 Hom.: 9021 Cov.: 32 AF XY: 0.311 AC XY: 23150 AN XY: 74430

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.366

Alfa AF: 0.267 Hom.: 2906

Bravo AF: 0.339

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.085
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4543123; hg19: chr4-38792524;