rs3773996

Positions:

• chr3-190518295-A-G

Variant summary

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

The NM_002182.4(IL1RAP):​c.-89+4076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,228 control chromosomes in the GnomAD database, including 488 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 0.045 (488 hom., cov: 31)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.-89+4076A>G		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.-89+4076A>G		intron_variant		1	NM_002182.4	P1

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6770 AN: 152110 Hom.: 486 Cov.: 31

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0445 AC: 6781 AN: 152228 Hom.: 488 Cov.: 31 AF XY: 0.0491 AC XY: 3658 AN XY: 74442

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0361 Hom.: 28

Bravo AF: 0.0440

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.84

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: rs3773996; hg19: chr3-190236084;