rs4571225

Positions:

• chr3-190606665-T-C

Variant summary

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

The NM_002182.4(IL1RAP):​c.350+2252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,258 control chromosomes in the GnomAD database, including 958 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 0.080 (958 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.350+2252T>C		intron_variant		ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.350+2252T>C		intron_variant		1	NM_002182.4	ENSP00000390541	P1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12163 AN: 152140 Hom.: 957 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0800 AC: 12181 AN: 152258 Hom.: 958 Cov.: 32 AF XY: 0.0768 AC XY: 5717 AN XY: 74440

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0482

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0657

Alfa AF: 0.0434 Hom.: 473

Bravo AF: 0.0883

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.88

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: rs4571225; hg19: chr3-190324454;