rs3796293

chr3-190614304-G-Achr3-190614304-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002182.4(IL1RAP):c.537+5123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,020 control chromosomes in the GnomAD database, including 30,143 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 0.62 (30143 hom., cov: 26)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.537+5123G>A		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.537+5123G>A		intron_variant		1	NM_002182.4	P1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93162 AN: 150900 Hom.: 30142 Cov.: 26

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.617 AC: 93181 AN: 151020 Hom.: 30143 Cov.: 26 AF XY: 0.627 AC XY: 46286 AN XY: 73804

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.620

Alfa AF: 0.537 Hom.: 2229

Bravo AF: 0.588

Asia WGS AF: 0.743 AC: 2586 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	0.64
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs3796293; hg19: chr3-190332093;