2-102344364-A-G

Position:

• chr2-102344364-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003856.4(IL1RL1):​c.*932A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 951,648 control chromosomes in the GnomAD database, including 29,447 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 0.30 (7742 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21705 hom.)
• Consequence: IL1RL1 NM_003856.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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]

IL1RL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.970+949A>G		intron_variant		ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.970+949A>G		intron_variant		1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45153 AN: 151974 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.227 AC: 181402 AN: 799556 Hom.: 21705 Cov.: 14 AF XY: 0.227 AC XY: 83917 AN XY: 370162

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.0801

Gnomad4 SAS exome AF: 0.0862

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.297 AC: 45210 AN: 152092 Hom.: 7742 Cov.: 32 AF XY: 0.295 AC XY: 21955 AN XY: 74342

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0958

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.274

Alfa AF: 0.240 Hom.: 4621

Bravo AF: 0.295

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2160203; hg19: chr2-102960824; COSMIC: COSV52113982; COSMIC: COSV52113982;