2-102110201-A-G

Variant names:

• chr2-102110201-A-G
• rs12712127
• ENST00000409929.5:c.-84+39668A>G

Variant summary

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

The NM_001320978.2(IL1R1):​c.-84+39668A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,872 control chromosomes in the GnomAD database, including 28,943 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 0.61 (28943 hom., cov: 31)
• Consequence: IL1R1 NM_001320978.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 25 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320978.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	NM_001320978.2		c.-84+39668A>G		intron	N/A	NP_001307907.1	P14778
	IL1R1	NM_001320980.2		c.-84+5329A>G		intron	N/A	NP_001307909.1	P14778
	IL1R1	NM_001288706.2		c.-84+39668A>G		intron	N/A	NP_001275635.1	B8ZZW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	ENST00000409929.5	TSL:1	c.-84+39668A>G		intron	N/A	ENSP00000386776.1	B8ZZW4
	IL1R1	ENST00000853658.1		c.-83-43740A>G		intron	N/A	ENSP00000523717.1
	IL1R1	ENST00000853659.1		c.-84+39668A>G		intron	N/A	ENSP00000523718.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92786 AN: 151750 Hom.: 28914 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.612 AC: 92870 AN: 151872 Hom.: 28943 Cov.: 31 AF XY: 0.608 AC XY: 45140 AN XY: 74200

African (AFR) AF: 0.700 AC: 28971 AN: 41378

American (AMR) AF: 0.620 AC: 9455 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1757 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1877 AN: 5160

South Asian (SAS) AF: 0.388 AC: 1864 AN: 4810

European-Finnish (FIN) AF: 0.642 AC: 6766 AN: 10534

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40107 AN: 67950

Other (OTH) AF: 0.586 AC: 1237 AN: 2112

Alfa AF: 0.591 Hom.: 113206

Bravo AF: 0.620

Asia WGS AF: 0.409 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.4
DANN	Benign	0.44
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12712127;

hg19: chr2-102726661;