NM_002182.4:c.65-7197C>A

Variant names:

• chr3-190596931-C-A
• rs3773953
• NM_002182.4:c.65-7197C>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.65-7197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,038 control chromosomes in the GnomAD database, including 720 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 0.093 (720 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.65-7197C>A		intron	N/A	NP_002173.1
	IL1RAP	NM_001167931.2		c.65-7197C>A		intron	N/A	NP_001161403.1
	IL1RAP	NM_001364879.1		c.65-7197C>A		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.65-7197C>A		intron	N/A	ENSP00000390541.1
	IL1RAP	ENST00000317757.8	TSL:1	c.65-7197C>A		intron	N/A	ENSP00000314807.3
	IL1RAP	ENST00000072516.7	TSL:1	c.65-7197C>A		intron	N/A	ENSP00000072516.3

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14145 AN: 151920 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0859

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

GnomAD4 genome AF: 0.0931 AC: 14154 AN: 152038 Hom.: 720 Cov.: 32 AF XY: 0.0910 AC XY: 6767 AN XY: 74326

African (AFR) AF: 0.118 AC: 4895 AN: 41450

American (AMR) AF: 0.0571 AC: 872 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 291 AN: 3462

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5180

South Asian (SAS) AF: 0.108 AC: 519 AN: 4814

European-Finnish (FIN) AF: 0.0641 AC: 678 AN: 10576

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6507 AN: 67962

Other (OTH) AF: 0.0859 AC: 181 AN: 2106

Alfa AF: 0.0896 Hom.: 1131

Bravo AF: 0.0932

Asia WGS AF: 0.0630 AC: 219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.19
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: rs3773953; hg19: chr3-190314720;