chr3-190628869-T-A

Variant names:

• chr3-190628869-T-A
• rs1024941
• NM_002182.4:c.903-481T>A

Variant summary

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

The NM_002182.4(IL1RAP):​c.903-481T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,084 control chromosomes in the GnomAD database, including 61,727 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 0.90 (61727 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.903-481T>A		intron_variant	Intron 8 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.903-481T>A		intron_variant	Intron 8 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136667 AN: 151966 Hom.: 61660 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.899 AC: 136793 AN: 152084 Hom.: 61727 Cov.: 32 AF XY: 0.903 AC XY: 67066 AN XY: 74310

African (AFR) AF: 0.971 AC: 40338 AN: 41560

American (AMR) AF: 0.908 AC: 13866 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3068 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5182

South Asian (SAS) AF: 0.950 AC: 4582 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8935 AN: 10534

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.854 AC: 58034 AN: 67926

Other (OTH) AF: 0.878 AC: 1857 AN: 2116

Alfa AF: 0.879 Hom.: 7323

Bravo AF: 0.905

Asia WGS AF: 0.967 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		0.044
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: rs1024941; hg19: chr3-190346658;