rs5743556

Variant names:

• chr4-38805230-A-G
• rs5743556
• ENST00000508535.1:n.304T>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 ENST00000508535.1(TLR1):​n.304T>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 0.146 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 ENST00000508535.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 20 publications found

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]

ENSG00000306984 (HGNC:):

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	ENST00000508535.1	n.304T>C		non_coding_transcript_exon_variant	Exon 1 of 3	4
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
ENSG00000306984	ENST00000822410.1	n.292-300A>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) 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

African (AFR) AF: 0.0344 AC: 1430 AN: 41540

American (AMR) AF: 0.174 AC: 2664 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2082 AN: 5166

South Asian (SAS) AF: 0.196 AC: 943 AN: 4816

European-Finnish (FIN) AF: 0.0838 AC: 888 AN: 10594

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12388 AN: 67992

Other (OTH) AF: 0.201 AC: 424 AN: 2108

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
PhyloP100		0.43
PromoterAI		-0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5743556; hg19: chr4-38806851;