rs5743556

Variant names:

• chr4-38805230-A-G
• rs5743556
• ENST00000508364.1:c.-186T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-38805230-A-G
• chr4-38805230-A-T

Variant summary

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

The ENST00000508364.1(TLR1):​c.-186T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,176 control chromosomes in the GnomAD database, including 2,245 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: 0.50 (1 hom.)
• Consequence: TLR1 ENST00000508364.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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 rank	MANE	Protein	UniProt
TLR1	XM_005262662.6	c.-389T>C		5_prime_UTR_variant	Exon 1 of 5		XP_005262719.1
TLR1	XM_011513742.4	c.-312T>C		5_prime_UTR_variant	Exon 1 of 4		XP_011512044.1
TLR1	XM_011513745.4	c.-220T>C		5_prime_UTR_variant	Exon 1 of 3		XP_011512047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000508364.1	c.-186T>C		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000424894.1
TLR1	ENST00000506146.5	c.-352-37T>C		intron_variant	Intron 1 of 5	4		ENSP00000423725.1
TLR1	ENST00000508535.1	n.304T>C		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22242 AN: 152054 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 2

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AC: 0 AN: 0

Gnomad4 NFE exome AF: 1.00 AC: 2 AN: 2

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22235 AN: 152172 Hom.: 2244 Cov.: 32 AF XY: 0.145 AC XY: 10784 AN XY: 74402

Gnomad4 AFR AF: 0.0344 AC: 0.0344247 AN: 0.0344247

Gnomad4 AMR AF: 0.174 AC: 0.174323 AN: 0.174323

Gnomad4 ASJ AF: 0.309 AC: 0.308535 AN: 0.308535

Gnomad4 EAS AF: 0.403 AC: 0.40302 AN: 0.40302

Gnomad4 SAS AF: 0.196 AC: 0.195806 AN: 0.195806

Gnomad4 FIN AF: 0.0838 AC: 0.083821 AN: 0.083821

Gnomad4 NFE AF: 0.182 AC: 0.182198 AN: 0.182198

Gnomad4 OTH AF: 0.201 AC: 0.201139 AN: 0.201139

Alfa AF: 0.152 Hom.: 285

Bravo AF: 0.152

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743556; hg19: chr4-38806851;