rs3773986

Variant names:

• chr3-190561126-G-A
• rs3773986
• NM_002182.4:c.-1-3163G>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.-1-3163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,162 control chromosomes in the GnomAD database, including 655 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 0.090 (655 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.-1-3163G>A		intron	N/A	NP_002173.1
	IL1RAP	NM_001167931.2		c.-1-3163G>A		intron	N/A	NP_001161403.1
	IL1RAP	NM_001364879.1		c.-1-3163G>A		intron	N/A	NP_001351808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.-1-3163G>A		intron	N/A	ENSP00000390541.1
	IL1RAP	ENST00000317757.8	TSL:1	c.-1-3163G>A		intron	N/A	ENSP00000314807.3
	IL1RAP	ENST00000072516.7	TSL:1	c.-1-3163G>A		intron	N/A	ENSP00000072516.3

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13639 AN: 152044 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.0898 AC: 13658 AN: 152162 Hom.: 655 Cov.: 32 AF XY: 0.0931 AC XY: 6928 AN XY: 74402

African (AFR) AF: 0.0951 AC: 3946 AN: 41512

American (AMR) AF: 0.0960 AC: 1468 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.123 AC: 635 AN: 5170

South Asian (SAS) AF: 0.106 AC: 512 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1379 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0737 AC: 5012 AN: 68006

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0821 Hom.: 1010

Bravo AF: 0.0898

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.043
DANN	Benign	0.38
PhyloP100		-1.6
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: rs3773986; hg19: chr3-190278915;