2-102165209-A-G

Position:

• chr2-102165209-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_000877.4(IL1R1):​c.391A>G​(p.Lys131Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.06

Genes affected

IL1R1 (HGNC:5993): (interleukin 1 receptor type 1) This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-102165209-A-G is Pathogenic according to our data. Variant chr2-102165209-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 2574622.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.12367776). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.391A>G	p.Lys131Glu	missense_variant	5/12	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.391A>G	p.Lys131Glu	missense_variant	5/12	1	NM_000877.4	ENSP00000386380	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Chronic recurrent multifocal osteomyelitis 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0094	T;.;T;.;.;T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.66	T;.;T;.;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;.;.;.;.;M;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.20	T;T;D;T;T;T;T
Sift4G	Benign	0.38	T;T;D;T;T;T;D
Polyphen		0.52	P;P;.;P;P;B;.
Vest4		0.30
MutPred		0.40		Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);Loss of ubiquitination at K131 (P = 0.0167);
MVP		0.60
MPC		0.95
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.38
gMVP		0.48

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.

Other links and lift over

hg19: chr2-102781669;