rs3773958

Variant names:

• chr3-190591814-A-C
• rs3773958
• NM_002182.4:c.65-12314A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-190591814-A-C
• chr3-190591814-A-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.65-12314A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,960 control chromosomes in the GnomAD database, including 2,809 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 0.17 (2809 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.65-12314A>C		intron_variant	Intron 3 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.65-12314A>C		intron_variant	Intron 3 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26010 AN: 151842 Hom.: 2816 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.171 AC: 26008 AN: 151960 Hom.: 2809 Cov.: 32 AF XY: 0.175 AC XY: 13010 AN XY: 74268

African (AFR) AF: 0.0483 AC: 2003 AN: 41494

American (AMR) AF: 0.211 AC: 3224 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2317 AN: 5144

South Asian (SAS) AF: 0.239 AC: 1146 AN: 4804

European-Finnish (FIN) AF: 0.192 AC: 2023 AN: 10538

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14075 AN: 67924

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.195 Hom.: 1590

Bravo AF: 0.162

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.43
PhyloP100		-0.44
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: rs3773958; hg19: chr3-190309603;