rs16865597

chr3-190557756-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002182.4(IL1RAP):c.-2+1540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,208 control chromosomes in the GnomAD database, including 2,592 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 0.16 (2592 hom., cov: 33)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4	c.-2+1540T>C		intron_variant		ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6	c.-2+1540T>C		intron_variant		1	NM_002182.4	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24623 AN: 152090 Hom.: 2579 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.162 AC: 24672 AN: 152208 Hom.: 2592 Cov.: 33 AF XY: 0.161 AC XY: 11998 AN XY: 74436

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.155

Alfa AF: 0.119 Hom.: 1546

Bravo AF: 0.173

Asia WGS AF: 0.171 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs16865597; hg19: chr3-190275545;