rs6444435

Variant names:

• chr3-190586016-A-G
• rs6444435
• NM_002182.4:c.65-18112A>G

Variant summary

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

The NM_002182.4(IL1RAP):​c.65-18112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,526 control chromosomes in the GnomAD database, including 13,564 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 0.41 (13564 hom., cov: 29)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.65-18112A>G		intron_variant	Intron 3 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.65-18112A>G		intron_variant	Intron 3 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62236 AN: 151408 Hom.: 13550 Cov.: 29

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.411 AC: 62297 AN: 151526 Hom.: 13564 Cov.: 29 AF XY: 0.422 AC XY: 31263 AN XY: 74016

African (AFR) AF: 0.434 AC: 17920 AN: 41264

American (AMR) AF: 0.500 AC: 7621 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3466

East Asian (EAS) AF: 0.800 AC: 4043 AN: 5052

South Asian (SAS) AF: 0.599 AC: 2861 AN: 4778

European-Finnish (FIN) AF: 0.420 AC: 4422 AN: 10540

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22965 AN: 67868

Other (OTH) AF: 0.439 AC: 925 AN: 2106

Alfa AF: 0.373 Hom.: 20562

Bravo AF: 0.416

Asia WGS AF: 0.713 AC: 2478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.065
DANN	Benign	0.76
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6444435; hg19: chr3-190303805;