chr4-38805678-C-T

Position:

• chr4-38805678-C-T

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-485G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152,206 control chromosomes in the GnomAD database, including 288 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 0.041 (288 hom., cov: 32)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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 (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	XM_005262662.6			upstream_gene_variant			XP_005262719.1
TLR1	XM_011513742.4			upstream_gene_variant			XP_011512044.1
TLR1	XM_011513745.4			upstream_gene_variant			XP_011512047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-485G>A		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6274 AN: 152058 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00856

Gnomad OTH AF: 0.0460

GnomAD4 exome AF: 0.0333 AC: 1 AN: 30 Hom.: 0 AF XY: 0.0455 AC XY: 1 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0413 AC: 6280 AN: 152176 Hom.: 288 Cov.: 32 AF XY: 0.0409 AC XY: 3044 AN XY: 74394

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0674

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.00856

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0211 Hom.: 17

Bravo AF: 0.0451

Asia WGS AF: 0.0850 AC: 298 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	5.1
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1873196; hg19: chr4-38807299;