rs1559018

chr3-190579294-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.64+14941A>G		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.64+14941A>G		intron_variant		1	NM_002182.4	P1

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

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.351

Alfa AF: 0.330 Hom.: 17448

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

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

Publications

LitVar

Other links and lift over

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