rs10513854

Variant names:

• chr3-190588085-C-T
• rs10513854
• NM_002182.4:c.65-16043C>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.65-16043C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,058 control chromosomes in the GnomAD database, including 2,675 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 0.18 (2675 hom., cov: 33)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.65-16043C>T		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.65-16043C>T		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.65-16043C>T		intron	N/A	NP_001351808.1	Q9NPH3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.65-16043C>T		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.65-16043C>T		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.65-16043C>T		intron	N/A	ENSP00000072516.3	Q9NPH3-1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27246 AN: 151940 Hom.: 2667 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.179 AC: 27287 AN: 152058 Hom.: 2675 Cov.: 33 AF XY: 0.180 AC XY: 13374 AN XY: 74336

African (AFR) AF: 0.255 AC: 10566 AN: 41468

American (AMR) AF: 0.203 AC: 3109 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3466

East Asian (EAS) AF: 0.167 AC: 861 AN: 5168

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4822

European-Finnish (FIN) AF: 0.0919 AC: 973 AN: 10584

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9652 AN: 67956

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.157 Hom.: 3692

Bravo AF: 0.194

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-1.1
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: rs10513854; hg19: chr3-190305874;