chr3-190645327-A-G

Variant names:

• chr3-190645327-A-G
• rs7650510
• NM_002182.4:c.1202-372A>G

Variant summary

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

The NM_002182.4(IL1RAP):​c.1202-372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,108 control chromosomes in the GnomAD database, including 4,565 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 0.24 (4565 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.1202-372A>G		intron	N/A	NP_002173.1
	IL1RAP	NM_001167931.2		c.1202-372A>G		intron	N/A	NP_001161403.1
	IL1RAP	NM_001364879.1		c.1202-372A>G		intron	N/A	NP_001351808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.1202-372A>G		intron	N/A	ENSP00000390541.1
	IL1RAP	ENST00000317757.8	TSL:1	c.1202-372A>G		intron	N/A	ENSP00000314807.3
	IL1RAP	ENST00000072516.7	TSL:1	c.1202-372A>G		intron	N/A	ENSP00000072516.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35928 AN: 151990 Hom.: 4553 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0279

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.236 AC: 35965 AN: 152108 Hom.: 4565 Cov.: 32 AF XY: 0.233 AC XY: 17336 AN XY: 74370

African (AFR) AF: 0.307 AC: 12741 AN: 41476

American (AMR) AF: 0.152 AC: 2321 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3472

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5180

South Asian (SAS) AF: 0.187 AC: 904 AN: 4830

European-Finnish (FIN) AF: 0.263 AC: 2779 AN: 10568

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15691 AN: 67978

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.228 Hom.: 11386

Bravo AF: 0.232

Asia WGS AF: 0.131 AC: 455 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.75
PhyloP100		-1.9
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: rs7650510; hg19: chr3-190363116;