3-190620623-G-A

Variant names:

• chr3-190620623-G-A
• rs1015704
• NM_002182.4:c.703+183G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.703+183G>A		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.703+183G>A		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.703+183G>A		intron	N/A	NP_001351808.1	Q9NPH3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.703+183G>A		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.703+183G>A		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.703+183G>A		intron	N/A	ENSP00000072516.3	Q9NPH3-1

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

African (AFR) AF: 0.404 AC: 16716 AN: 41362

American (AMR) AF: 0.603 AC: 9198 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2491 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4185 AN: 5160

South Asian (SAS) AF: 0.703 AC: 3381 AN: 4806

European-Finnish (FIN) AF: 0.815 AC: 8617 AN: 10574

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46497 AN: 67930

Other (OTH) AF: 0.618 AC: 1303 AN: 2108

Alfa AF: 0.543 Hom.: 5966

Bravo AF: 0.584

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.70
DANN	Benign	0.39
PhyloP100		-0.36
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: rs1015704; hg19: chr3-190338412;