2-102172314-G-A

Variant names:

• chr2-102172314-G-A
• rs3771200
• NM_000877.4:c.840-373G>A

Variant summary

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

The NM_000877.4(IL1R1):​c.840-373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 984,326 control chromosomes in the GnomAD database, including 74,869 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8185 hom., cov: 30)
  • Exomes 𝑓: 0.40 (66684 hom.)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 14 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.840-373G>A		intron_variant	Intron 8 of 11	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.840-373G>A		intron_variant	Intron 8 of 11	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47284 AN: 151762 Hom.: 8184 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.397 AC: 330219 AN: 832446 Hom.: 66684 Cov.: 28 AF XY: 0.398 AC XY: 152942 AN XY: 384420

African (AFR) AF: 0.134 AC: 2114 AN: 15782

American (AMR) AF: 0.286 AC: 281 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1730 AN: 5144

East Asian (EAS) AF: 0.432 AC: 1567 AN: 3630

South Asian (SAS) AF: 0.368 AC: 6056 AN: 16450

European-Finnish (FIN) AF: 0.402 AC: 111 AN: 276

Middle Eastern (MID) AF: 0.295 AC: 475 AN: 1610

European-Non Finnish (NFE) AF: 0.404 AC: 307571 AN: 761312

Other (OTH) AF: 0.378 AC: 10314 AN: 27260

GnomAD4 genome AF: 0.311 AC: 47289 AN: 151880 Hom.: 8185 Cov.: 30 AF XY: 0.312 AC XY: 23155 AN XY: 74200

African (AFR) AF: 0.151 AC: 6263 AN: 41458

American (AMR) AF: 0.273 AC: 4163 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2227 AN: 5146

South Asian (SAS) AF: 0.367 AC: 1761 AN: 4804

European-Finnish (FIN) AF: 0.390 AC: 4096 AN: 10506

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.390 AC: 26478 AN: 67934

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.363 Hom.: 44561

Bravo AF: 0.295

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.65
PhyloP100		-0.62
Mutation Taster		=100/0	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: rs3771200; hg19: chr2-102788774;