rs1921622

Variant names:

• chr2-102349607-G-A
• rs1921622
• NM_016232.5:c.1285+361G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102349607-G-A
• chr2-102349607-G-T

Variant summary

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

The NM_016232.5(IL1RL1):​c.1285+361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,032 control chromosomes in the GnomAD database, including 14,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.42 (14831 hom., cov: 32)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0550
• Publications: 49 publications found

Genes affected

IL1RL1 (HGNC:5998): (interleukin 1 receptor like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016232.5. 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
	IL1RL1	NM_016232.5	MANE Select	c.1285+361G>A		intron	N/A	NP_057316.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1285+361G>A		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000908526.1		c.1285+361G>A		intron	N/A	ENSP00000578585.1
	IL1RL1	ENST00000908527.1		c.1285+361G>A		intron	N/A	ENSP00000578586.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64509 AN: 151914 Hom.: 14831 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.424 AC: 64532 AN: 152032 Hom.: 14831 Cov.: 32 AF XY: 0.421 AC XY: 31319 AN XY: 74308

African (AFR) AF: 0.251 AC: 10408 AN: 41456

American (AMR) AF: 0.378 AC: 5770 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1627 AN: 3460

East Asian (EAS) AF: 0.466 AC: 2413 AN: 5180

South Asian (SAS) AF: 0.453 AC: 2179 AN: 4814

European-Finnish (FIN) AF: 0.477 AC: 5026 AN: 10542

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35573 AN: 67976

Other (OTH) AF: 0.460 AC: 973 AN: 2114

Alfa AF: 0.488 Hom.: 31550

Bravo AF: 0.408

Asia WGS AF: 0.458 AC: 1596 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Ascending aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		-0.055
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: rs1921622; hg19: chr2-102966067;