rs6765375

Positions:

• chr3-190609963-C-A
• chr3-190609963-C-T

Variant summary

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

The NM_002182.4(IL1RAP):​c.537+782C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,032 control chromosomes in the GnomAD database, including 28,271 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 0.58 (28271 hom., cov: 32)
• 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]

IL1RAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAP	NM_002182.4	c.537+782C>A		intron_variant		ENST00000447382.6	NP_002173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAP	ENST00000447382.6	c.537+782C>A		intron_variant		1	NM_002182.4	ENSP00000390541.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87907 AN: 151910 Hom.: 28276 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.578 AC: 87917 AN: 152032 Hom.: 28271 Cov.: 32 AF XY: 0.592 AC XY: 44032 AN XY: 74340

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.592

Alfa AF: 0.621 Hom.: 3879

Bravo AF: 0.546

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.59

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: rs6765375; hg19: chr3-190327752;