NM_003854.4:c.724+134G>C

Variant names:

• chr2-102212308-G-C
• rs1922290
• NM_003854.4:c.724+134G>C

Variant summary

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

The NM_003854.4(IL1RL2):​c.724+134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 615,744 control chromosomes in the GnomAD database, including 33,359 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 0.28 (6614 hom., cov: 32)
  • Exomes 𝑓: 0.34 (26745 hom.)
• Consequence: IL1RL2 NM_003854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 6 publications found

Genes affected

IL1RL2 (HGNC:5999): (interleukin 1 receptor like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. An experiment with transient gene expression demonstrated that this receptor was incapable of binding to interleukin 1 alpha and interleukin 1 beta with high affinity. This gene and four other interleukin 1 receptor family genes, including interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 1 (IL1RL1), and interleukin 18 receptor 1 (IL18R1), form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003854.4. 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
	IL1RL2	NM_003854.4	MANE Select	c.724+134G>C		intron	N/A	NP_003845.2
	IL1RL2	NM_001351446.2		c.724+134G>C		intron	N/A	NP_001338375.1
	IL1RL2	NM_001351447.1		c.370+134G>C		intron	N/A	NP_001338376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL2	ENST00000264257.7	TSL:1 MANE Select	c.724+134G>C		intron	N/A	ENSP00000264257.2
	IL1RL2	ENST00000441515.3	TSL:1	c.370+134G>C		intron	N/A	ENSP00000413348.2
	IL1RL2	ENST00000481806.1	TSL:5	n.386+134G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42633 AN: 151880 Hom.: 6612 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.335 AC: 155532 AN: 463746 Hom.: 26745 AF XY: 0.337 AC XY: 82806 AN XY: 245594

African (AFR) AF: 0.141 AC: 1809 AN: 12864

American (AMR) AF: 0.229 AC: 4917 AN: 21484

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 3834 AN: 13738

East Asian (EAS) AF: 0.367 AC: 11079 AN: 30202

South Asian (SAS) AF: 0.371 AC: 15861 AN: 42748

European-Finnish (FIN) AF: 0.360 AC: 11015 AN: 30596

Middle Eastern (MID) AF: 0.256 AC: 521 AN: 2032

European-Non Finnish (NFE) AF: 0.346 AC: 98262 AN: 284346

Other (OTH) AF: 0.320 AC: 8234 AN: 25736

GnomAD4 genome AF: 0.281 AC: 42637 AN: 151998 Hom.: 6614 Cov.: 32 AF XY: 0.284 AC XY: 21063 AN XY: 74290

African (AFR) AF: 0.144 AC: 5982 AN: 41482

American (AMR) AF: 0.247 AC: 3776 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1990 AN: 5170

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4814

European-Finnish (FIN) AF: 0.348 AC: 3665 AN: 10524

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23405 AN: 67958

Other (OTH) AF: 0.286 AC: 603 AN: 2108

Alfa AF: 0.208 Hom.: 556

Bravo AF: 0.265

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.34
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: rs1922290; hg19: chr2-102828768; COSMIC: COSV51816311;