Variant 3-190620339-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002182.4(IL1RAP):c.602T>A(p.Ile201Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL1RAP
NM_002182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_002182.4 linkuse as main transcript	c.602T>A	p.Ile201Asn	missense_variant	6/12	ENST00000447382.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000447382.6 linkuse as main transcript	c.602T>A	p.Ile201Asn	missense_variant	6/12	1	NM_002182.4	P1	Q9NPH3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.602T>A (p.I201N) alteration is located in exon 6 (coding exon 4) of the IL1RAP gene. This alteration results from a T to A substitution at nucleotide position 602, causing the isoleucine (I) at amino acid position 201 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;T;.;T;.;.;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.56

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;M;.;M;M;M;M

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.50

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.15

T;T;T;D;D;D;T;T;T

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D;D;D

Vest4

0.51

MutPred

0.62

Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);.;Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);Loss of stability (P = 0.0301);

MVP

0.66

MPC

0.69

ClinPred

0.32

GERP RS

-1.6

Varity_R

0.18

gMVP

0.92

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over