rs11714779

Positions:

• chr3-190582640-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002182.4(IL1RAP):​c.64+18287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 152,156 control chromosomes in the GnomAD database, including 70 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 0.022 (70 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.022 (3351/152156) while in subpopulation NFE AF= 0.0336 (2288/67998). AF 95% confidence interval is 0.0325. There are 70 homozygotes in gnomad4. There are 1631 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 70 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.64+18287G>A		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.64+18287G>A		intron_variant		1	NM_002182.4	P1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3353 AN: 152038 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.00440

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0220 AC: 3351 AN: 152156 Hom.: 70 Cov.: 32 AF XY: 0.0219 AC XY: 1631 AN XY: 74372

Gnomad4 AFR AF: 0.00438

Gnomad4 AMR AF: 0.00766

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.00789

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0279 Hom.: 31

Bravo AF: 0.0167

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.43

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: rs11714779; hg19: chr3-190300429;