rs1559018

Variant names:

• chr3-190579294-A-G
• rs1559018
• NM_002182.4:c.64+14941A>G

Variant summary

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

The NM_002182.4(IL1RAP):​c.64+14941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,020 control chromosomes in the GnomAD database, including 9,541 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 0.35 (9541 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 17 publications found

Genes affected

IL1RAP (HGNC:5995): (interleukin 1 receptor accessory protein) This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

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 = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.64+14941A>G		intron_variant	Intron 3 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.64+14941A>G		intron_variant	Intron 3 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53029 AN: 151902 Hom.: 9530 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.349 AC: 53077 AN: 152020 Hom.: 9541 Cov.: 32 AF XY: 0.351 AC XY: 26099 AN XY: 74334

African (AFR) AF: 0.350 AC: 14496 AN: 41452

American (AMR) AF: 0.414 AC: 6323 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2649 AN: 5170

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4822

European-Finnish (FIN) AF: 0.370 AC: 3903 AN: 10560

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22047 AN: 67970

Other (OTH) AF: 0.351 AC: 742 AN: 2114

Alfa AF: 0.332 Hom.: 27567

Bravo AF: 0.355

Asia WGS AF: 0.413 AC: 1441 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	2.7
DANN	Benign	0.41
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs1559018; hg19: chr3-190297083; COSMIC: COSV50763177;