chr3-190534846-G-T

Variant names:

• chr3-190534846-G-T
• rs9290936
• NM_002182.4:c.-89+20627G>T

Variant summary

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

The NM_002182.4(IL1RAP):​c.-89+20627G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 149,884 control chromosomes in the GnomAD database, including 3,472 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 0.20 (3472 hom., cov: 29)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 21 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.-89+20627G>T		intron_variant	Intron 1 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.-89+20627G>T		intron_variant	Intron 1 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29333 AN: 149776 Hom.: 3461 Cov.: 29

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.196 AC: 29377 AN: 149884 Hom.: 3472 Cov.: 29 AF XY: 0.196 AC XY: 14345 AN XY: 73064

African (AFR) AF: 0.302 AC: 12154 AN: 40298

American (AMR) AF: 0.167 AC: 2507 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3460

East Asian (EAS) AF: 0.423 AC: 2152 AN: 5082

South Asian (SAS) AF: 0.168 AC: 803 AN: 4772

European-Finnish (FIN) AF: 0.135 AC: 1374 AN: 10146

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9040 AN: 67782

Other (OTH) AF: 0.198 AC: 414 AN: 2090

Alfa AF: 0.159 Hom.: 8945

Bravo AF: 0.204

Asia WGS AF: 0.319 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		-0.43
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: rs9290936; hg19: chr3-190252635;