rs16865597

Variant names:

• chr3-190557756-T-C
• rs16865597
• NM_002182.4:c.-2+1540T>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.-2+1540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,208 control chromosomes in the GnomAD database, including 2,592 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 0.16 (2592 hom., cov: 33)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.-2+1540T>C		intron_variant	Intron 2 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.-2+1540T>C		intron_variant	Intron 2 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24623 AN: 152090 Hom.: 2579 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.162 AC: 24672 AN: 152208 Hom.: 2592 Cov.: 33 AF XY: 0.161 AC XY: 11998 AN XY: 74436

African (AFR) AF: 0.301 AC: 12472 AN: 41502

American (AMR) AF: 0.145 AC: 2216 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.126 AC: 654 AN: 5190

South Asian (SAS) AF: 0.174 AC: 839 AN: 4828

European-Finnish (FIN) AF: 0.0763 AC: 810 AN: 10618

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6824 AN: 67992

Other (OTH) AF: 0.155 AC: 329 AN: 2116

Alfa AF: 0.124 Hom.: 3872

Bravo AF: 0.173

Asia WGS AF: 0.171 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.26
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: rs16865597; hg19: chr3-190275545;