chr2-102157594-G-A

Variant names:

• chr2-102157594-G-A
• rs2287047
• NM_000877.4:c.-6-125G>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.-6-125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 680,202 control chromosomes in the GnomAD database, including 41,139 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 0.38 (12498 hom., cov: 32)
  • Exomes 𝑓: 0.32 (28641 hom.)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 34 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.-6-125G>A		intron_variant	Intron 2 of 11	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.-6-125G>A		intron_variant	Intron 2 of 11	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58250 AN: 151934 Hom.: 12478 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.320 AC: 168816 AN: 528150 Hom.: 28641 AF XY: 0.319 AC XY: 91319 AN XY: 286324

African (AFR) AF: 0.587 AC: 7984 AN: 13606

American (AMR) AF: 0.278 AC: 6617 AN: 23836

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 7346 AN: 18612

East Asian (EAS) AF: 0.481 AC: 15212 AN: 31610

South Asian (SAS) AF: 0.309 AC: 17408 AN: 56344

European-Finnish (FIN) AF: 0.264 AC: 10262 AN: 38830

Middle Eastern (MID) AF: 0.326 AC: 1275 AN: 3914

European-Non Finnish (NFE) AF: 0.298 AC: 93053 AN: 312176

Other (OTH) AF: 0.331 AC: 9659 AN: 29222

GnomAD4 genome AF: 0.384 AC: 58327 AN: 152052 Hom.: 12498 Cov.: 32 AF XY: 0.381 AC XY: 28322 AN XY: 74336

African (AFR) AF: 0.587 AC: 24337 AN: 41474

American (AMR) AF: 0.316 AC: 4820 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2153 AN: 5176

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2764 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20142 AN: 67976

Other (OTH) AF: 0.354 AC: 746 AN: 2108

Alfa AF: 0.329 Hom.: 6658

Bravo AF: 0.396

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.34
PhyloP100		-0.36
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: rs2287047; hg19: chr2-102774054; COSMIC: COSV52105345;