rs4624663

Positions:

• chr4-38796255-T-C

Variant summary

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

The NM_003263.4(TLR1):​c.*216A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 546,750 control chromosomes in the GnomAD database, including 368 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 0.039 (165 hom., cov: 32)
  • Exomes 𝑓: 0.026 (203 hom.)
• Consequence: TLR1 NM_003263.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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]

TLR1 (HGNC:):

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 = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4	c.*216A>G		splice_region_variant	4/4	ENST00000308979.7	NP_003254.2
TLR1	NM_003263.4	c.*216A>G		3_prime_UTR_variant	4/4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.*216A>G		splice_region_variant	4/4	1	NM_003263.4	ENSP00000354932.2
TLR1	ENST00000308979	c.*216A>G		3_prime_UTR_variant	4/4	1	NM_003263.4	ENSP00000354932.2
TLR1	ENST00000505744.5	n.235+4602A>G		intron_variant		3
TLR1	ENST00000502213.6	c.*216A>G		downstream_gene_variant		1		ENSP00000421259.1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5942 AN: 152186 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0439

GnomAD4 exome AF: 0.0262 AC: 10322 AN: 394446 Hom.: 203 Cov.: 5 AF XY: 0.0253 AC XY: 5190 AN XY: 205238

Gnomad4 AFR exome AF: 0.0743

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0586

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.00923

Gnomad4 FIN exome AF: 0.0153

Gnomad4 NFE exome AF: 0.0284

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0391 AC: 5952 AN: 152304 Hom.: 165 Cov.: 32 AF XY: 0.0376 AC XY: 2799 AN XY: 74480

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0316 Hom.: 106

Bravo AF: 0.0415

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
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: rs4624663; hg19: chr4-38797876;