rs3917225

Variant names:

• chr2-102152842-A-G
• rs3917225
• NM_000877.4:c.-83-1099A>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.-83-1099A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,958 control chromosomes in the GnomAD database, including 11,662 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 0.36 (11662 hom., cov: 31)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 36 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.-83-1099A>G		intron_variant	Intron 1 of 11	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.-83-1099A>G		intron_variant	Intron 1 of 11	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54414 AN: 151840 Hom.: 11660 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.358 AC: 54416 AN: 151958 Hom.: 11662 Cov.: 31 AF XY: 0.366 AC XY: 27145 AN XY: 74254

African (AFR) AF: 0.112 AC: 4665 AN: 41494

American (AMR) AF: 0.452 AC: 6900 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2038 AN: 5144

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4818

European-Finnish (FIN) AF: 0.596 AC: 6262 AN: 10508

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.447 AC: 30390 AN: 67934

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.406 Hom.: 10126

Bravo AF: 0.340

Asia WGS AF: 0.374 AC: 1302 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	2.3
DANN	Benign	0.71
PhyloP100		0.14
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: rs3917225; hg19: chr2-102769302; COSMIC: COSV52107985; COSMIC: COSV52107985;