2-102157782-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000877.4(IL1R1):c.58G>A(p.Ala20Thr) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087237835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.58G>A	p.Ala20Thr	missense_variant	3/12	ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.58G>A	p.Ala20Thr	missense_variant	3/12	1	NM_000877.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.58G>A (p.A20T) alteration is located in exon 2 (coding exon 1) of the IL1R1 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.034	T;T;.;T;.;.;T;.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.70	T;T;.;T;.;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.087	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.91	N;N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.31	T;T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.044	D;T;T;T;T;T;T;T;T;T
Polyphen		0.16, 0.14, 0.083	.;B;B;.;B;.;.;B;B;.
Vest4		0.14, 0.085, 0.11, 0.086, 0.067
MutPred		0.29		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.29
MPC		0.24
ClinPred		0.18	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr2-102774242;