chr2-102166249-C-T

Variant names:

• chr2-102166249-C-T
• NM_000877.4:c.623C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000877.4(IL1R1):​c.623C>T​(p.Pro208Leu) 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. 14/22 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: -2.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07982013).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	NM_000877.4	MANE Select	c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	NP_000868.1	P14778
	IL1R1	NM_001320978.2		c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	NP_001307907.1	P14778
	IL1R1	NM_001320980.2		c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	NP_001307909.1	P14778

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	ENST00000410023.6	TSL:1 MANE Select	c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	ENSP00000386380.1	P14778
	IL1R1	ENST00000409929.5	TSL:1	c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	ENSP00000386776.1	B8ZZW4
	IL1R1	ENST00000853658.1		c.623C>T	p.Pro208Leu	missense	Exon 6 of 12	ENSP00000523717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.069
DANN	Benign	0.79
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-2.2
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.31	B
Vest4		0.26
MutPred		0.54		Gain of sheet (P = 0.0344)
MVP		0.20
MPC		0.32
ClinPred		0.22	T
GERP RS		-12
Varity_R		0.13
gMVP		0.51
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-102782709;