2-102175549-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000877.4(IL1R1):c.1207T>A(p.Cys403Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.235

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]

IL1R1-AS1 (HGNC:53898): (IL1R1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041908294).
• BP6: Variant 2-102175549-T-A is Benign according to our data. Variant chr2-102175549-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2490296.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.1207T>A	p.Cys403Ser	missense_variant	11/12	ENST00000410023.6
IL1R1-AS1	NR_174960.1	n.306-2852A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.1207T>A	p.Cys403Ser	missense_variant	11/12	1	NM_000877.4	P1
IL1R1-AS1	ENST00000428188.1	n.306-2852A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	11
Dann	Benign	0.85
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.042	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.010	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.65	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B
Vest4		0.027
MutPred		0.59		Gain of disorder (P = 3e-04);Gain of disorder (P = 3e-04);.;Gain of disorder (P = 3e-04);Gain of disorder (P = 3e-04);
MVP		0.14
MPC		0.30
ClinPred		0.27	T
GERP RS		4.0
Varity_R		0.087
gMVP		0.37

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: chr2-102792009;