rs45482391

Variant names:

• chr4-38803220-T-A
• rs45482391
• NM_003263.4:c.-160+1086A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003263.4(TLR1):​c.-160+1086A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 152,188 control chromosomes in the GnomAD database, including 56 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 0.022 (56 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-160+1086A>T		intron_variant	Intron 2 of 3	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-160+1086A>T		intron_variant	Intron 2 of 3	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3390 AN: 152070 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.00651

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0223 AC: 3393 AN: 152188 Hom.: 56 Cov.: 32 AF XY: 0.0234 AC XY: 1743 AN XY: 74406

African (AFR) AF: 0.0203 AC: 844 AN: 41528

American (AMR) AF: 0.0347 AC: 531 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.0105 AC: 54 AN: 5164

South Asian (SAS) AF: 0.0883 AC: 425 AN: 4812

European-Finnish (FIN) AF: 0.00651 AC: 69 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1259 AN: 68000

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0182 Hom.: 6

Bravo AF: 0.0227

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs45482391; hg19: chr4-38804841;