rs5743557

Positions:

• chr4-38805206-G-A

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,214 control chromosomes in the GnomAD database, including 2,244 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 0.15 (2244 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR1 ENST00000506146.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	XM_005262662.6	c.-365C>T		5_prime_UTR_variant	1/5		XP_005262719.1
TLR1	XM_011513742.4	c.-288C>T		5_prime_UTR_variant	1/4		XP_011512044.1
TLR1	XM_011513745.4	c.-196C>T		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.-162C>T		5_prime_UTR_variant	1/2	4		ENSP00000424894
TLR1	ENST00000506146.5	c.-352-13C>T		splice_polypyrimidine_tract_variant, intron_variant		4		ENSP00000423725
TLR1	ENST00000508535.1	n.328C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22256 AN: 152096 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.203

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.146 AC: 22249 AN: 152214 Hom.: 2244 Cov.: 32 AF XY: 0.145 AC XY: 10790 AN XY: 74406

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.201

Alfa AF: 0.155 Hom.: 374

Bravo AF: 0.152

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743557; hg19: chr4-38806827;