rs4571225

Variant names:

• chr3-190606665-T-C
• rs4571225
• NM_002182.4:c.350+2252T>C

Variant summary

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

The NM_002182.4(IL1RAP):​c.350+2252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,258 control chromosomes in the GnomAD database, including 958 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 0.080 (958 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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.350+2252T>C		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.350+2252T>C		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.350+2252T>C		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.350+2252T>C		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.350+2252T>C		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.350+2252T>C		intron	N/A	ENSP00000072516.3	Q9NPH3-1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12163 AN: 152140 Hom.: 957 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0800 AC: 12181 AN: 152258 Hom.: 958 Cov.: 32 AF XY: 0.0768 AC XY: 5717 AN XY: 74440

African (AFR) AF: 0.202 AC: 8371 AN: 41524

American (AMR) AF: 0.0482 AC: 736 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4830

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0381 AC: 2591 AN: 68022

Other (OTH) AF: 0.0657 AC: 139 AN: 2116

Alfa AF: 0.0528 Hom.: 1227

Bravo AF: 0.0883

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.88
PhyloP100		-0.079
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: rs4571225; hg19: chr3-190324454;