2-102165189-C-G

Variant names:

• chr2-102165189-C-G
• rs2228139
• NM_000877.4:c.371C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000877.4(IL1R1):​c.371C>G​(p.Ala124Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 1,592,528 control chromosomes in the GnomAD database, including 3,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (338 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3170 hom.)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 40 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015969872).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.371C>G	p.Ala124Gly	missense_variant	Exon 5 of 12	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.371C>G	p.Ala124Gly	missense_variant	Exon 5 of 12	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9029 AN: 151974 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0536

GnomAD2 exomes AF: 0.0557 AC: 12318 AN: 221012 AF XY: 0.0543

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.0406

Gnomad ASJ exome AF: 0.0486

Gnomad EAS exome AF: 0.000440

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0705

Gnomad OTH exome AF: 0.0585

GnomAD4 exome AF: 0.0625 AC: 90014 AN: 1440440 Hom.: 3170 Cov.: 30 AF XY: 0.0609 AC XY: 43631 AN XY: 715898

African (AFR) AF: 0.0487 AC: 1577 AN: 32354

American (AMR) AF: 0.0404 AC: 1592 AN: 39432

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 1129 AN: 25598

East Asian (EAS) AF: 0.000183 AC: 7 AN: 38274

South Asian (SAS) AF: 0.00906 AC: 754 AN: 83236

European-Finnish (FIN) AF: 0.106 AC: 5476 AN: 51594

Middle Eastern (MID) AF: 0.0306 AC: 171 AN: 5588

European-Non Finnish (NFE) AF: 0.0688 AC: 75959 AN: 1104710

Other (OTH) AF: 0.0561 AC: 3349 AN: 59654

GnomAD4 genome AF: 0.0593 AC: 9026 AN: 152088 Hom.: 338 Cov.: 32 AF XY: 0.0605 AC XY: 4496 AN XY: 74334

African (AFR) AF: 0.0481 AC: 1996 AN: 41502

American (AMR) AF: 0.0539 AC: 823 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0679 AC: 4614 AN: 67954

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0613 Hom.: 175

Bravo AF: 0.0550

ESP6500AA AF: 0.0481 AC: 212

ESP6500EA AF: 0.0642 AC: 552

ExAC AF: 0.0491 AC: 5959

Asia WGS AF: 0.00780 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.1
DANN	Benign	0.48
DEOGEN2	Benign	0.013	T;.;T;.;.;T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.61	T;.;T;.;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.57	.;.;.;.;.;N;.
PhyloP100		-0.71
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N;N;N;N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.42	T;T;T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;B;B;.
Vest4		0.056
MPC		0.25
ClinPred		0.0029	T
GERP RS		1.3
Varity_R		0.19
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2228139; hg19: chr2-102781649; COSMIC: COSV52106057; COSMIC: COSV52106057;