rs12053868

Variant names:

• chr3-190582215-A-G
• rs12053868
• NM_002182.4:c.64+17862A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-190582215-A-G
• chr3-190582215-A-T

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+17862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 151,776 control chromosomes in the GnomAD database, including 630 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 0.082 (630 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 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.64+17862A>G		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.64+17862A>G		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.64+17862A>G		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.64+17862A>G		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.64+17862A>G		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.64+17862A>G		intron	N/A	ENSP00000072516.3	Q9NPH3-1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12427 AN: 151668 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.0819 AC: 12426 AN: 151776 Hom.: 630 Cov.: 32 AF XY: 0.0813 AC XY: 6029 AN XY: 74166

African (AFR) AF: 0.0210 AC: 867 AN: 41358

American (AMR) AF: 0.0785 AC: 1198 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3468

East Asian (EAS) AF: 0.142 AC: 734 AN: 5162

South Asian (SAS) AF: 0.0692 AC: 332 AN: 4800

European-Finnish (FIN) AF: 0.0872 AC: 915 AN: 10492

Middle Eastern (MID) AF: 0.0448 AC: 13 AN: 290

European-Non Finnish (NFE) AF: 0.114 AC: 7755 AN: 67930

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.0942 Hom.: 649

Bravo AF: 0.0784

Asia WGS AF: 0.0910 AC: 314 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	0.0080
DANN	Benign	0.50
PhyloP100		-2.7
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: rs12053868; hg19: chr3-190300004;