rs3917299

Variant names:

• chr2-102169626-A-G
• rs3917299
• NM_000877.4:c.721+963A>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.721+963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,336 control chromosomes in the GnomAD database, including 460 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 0.071 (460 hom., cov: 33)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	NM_000877.4	MANE Select	c.721+963A>G		intron	N/A	NP_000868.1
	IL1R1	NM_001320978.2		c.721+963A>G		intron	N/A	NP_001307907.1
	IL1R1	NM_001320980.2		c.721+963A>G		intron	N/A	NP_001307909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	ENST00000410023.6	TSL:1 MANE Select	c.721+963A>G		intron	N/A	ENSP00000386380.1
	IL1R1	ENST00000409929.5	TSL:1	c.721+963A>G		intron	N/A	ENSP00000386776.1
	IL1R1	ENST00000409288.5	TSL:5	c.721+963A>G		intron	N/A	ENSP00000386478.1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10742 AN: 152218 Hom.: 463 Cov.: 33

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0705 AC: 10743 AN: 152336 Hom.: 460 Cov.: 33 AF XY: 0.0712 AC XY: 5303 AN XY: 74496

African (AFR) AF: 0.0853 AC: 3545 AN: 41572

American (AMR) AF: 0.0597 AC: 915 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0685 AC: 4663 AN: 68030

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0657 Hom.: 96

Bravo AF: 0.0682

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.61
PhyloP100		-0.71
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: rs3917299; hg19: chr2-102786086;