rs2161060

Variant names:

• chr3-190616826-C-T
• rs2161060
• NM_002182.4:c.538-3449C>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.538-3449C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,228 control chromosomes in the GnomAD database, including 61,653 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 0.90 (61653 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.538-3449C>T		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.538-3449C>T		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.538-3449C>T		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.538-3449C>T		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.538-3449C>T		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.538-3449C>T		intron	N/A	ENSP00000072516.3	Q9NPH3-1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136623 AN: 152110 Hom.: 61586 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.898 AC: 136750 AN: 152228 Hom.: 61653 Cov.: 32 AF XY: 0.905 AC XY: 67343 AN XY: 74432

African (AFR) AF: 0.968 AC: 40237 AN: 41548

American (AMR) AF: 0.892 AC: 13626 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3125 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5182

South Asian (SAS) AF: 0.940 AC: 4535 AN: 4826

European-Finnish (FIN) AF: 0.924 AC: 9796 AN: 10602

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.845 AC: 57449 AN: 68000

Other (OTH) AF: 0.867 AC: 1832 AN: 2114

Alfa AF: 0.877 Hom.: 21016

Bravo AF: 0.897

Asia WGS AF: 0.964 AC: 3353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.22
DANN	Benign	0.61
PhyloP100		-0.60
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2161060;

hg19: chr3-190334615;