chr3-190516515-T-C

Variant names:

• chr3-190516515-T-C
• rs6800609
• NM_002182.4:c.-89+2296T>C

Variant summary

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

The NM_002182.4(IL1RAP):​c.-89+2296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,206 control chromosomes in the GnomAD database, including 1,963 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 0.12 (1963 hom., cov: 32)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.-89+2296T>C		intron_variant	Intron 1 of 11	ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.-89+2296T>C		intron_variant	Intron 1 of 11	1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18269 AN: 152088 Hom.: 1957 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.120 AC: 18302 AN: 152206 Hom.: 1963 Cov.: 32 AF XY: 0.123 AC XY: 9189 AN XY: 74424

African (AFR) AF: 0.223 AC: 9266 AN: 41504

American (AMR) AF: 0.116 AC: 1767 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2416 AN: 5178

South Asian (SAS) AF: 0.153 AC: 738 AN: 4824

European-Finnish (FIN) AF: 0.0775 AC: 822 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2829 AN: 68020

Other (OTH) AF: 0.116 AC: 244 AN: 2110

Alfa AF: 0.0652 Hom.: 911

Bravo AF: 0.128

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		0.50
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: rs6800609; hg19: chr3-190234304;