rs1015704

chr3-190620623-G-Achr3-190620623-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002182.4(IL1RAP):c.703+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,882 control chromosomes in the GnomAD database, including 30,098 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 0.61 (30098 hom., cov: 31)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.703+183G>A		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.703+183G>A		intron_variant		1	NM_002182.4	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93145 AN: 151762 Hom.: 30097 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.613 AC: 93164 AN: 151882 Hom.: 30098 Cov.: 31 AF XY: 0.623 AC XY: 46291 AN XY: 74266

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.618

Alfa AF: 0.611 Hom.: 4390

Bravo AF: 0.584

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.70
Dann	Benign	0.39

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: rs1015704; hg19: chr3-190338412;