chr2-102340888-C-T

Variant names:

• chr2-102340888-C-T
• rs10173081
• NM_016232.5:c.610+60C>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.610+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,354,726 control chromosomes in the GnomAD database, including 15,464 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 0.17 (2647 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12817 hom.)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 33 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 (AFR) allele frequency at 95% confidence interval = 0.259 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.610+60C>T		intron	N/A	NP_057316.3
	IL1RL1	NM_003856.4		c.610+60C>T		intron	N/A	NP_003847.2
	IL1RL1	NM_001282408.2		c.259+60C>T		intron	N/A	NP_001269337.1	Q01638-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.610+60C>T		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000311734.6	TSL:1	c.610+60C>T		intron	N/A	ENSP00000310371.2	Q01638-2
	IL1RL1	ENST00000427077.1	TSL:1	n.610+60C>T		intron	N/A	ENSP00000391120.1	Q01638-3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26509 AN: 151924 Hom.: 2644 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.141 AC: 170057 AN: 1202684 Hom.: 12817 AF XY: 0.140 AC XY: 83491 AN XY: 596870

African (AFR) AF: 0.276 AC: 6702 AN: 24270

American (AMR) AF: 0.0915 AC: 1963 AN: 21458

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 4252 AN: 19066

East Asian (EAS) AF: 0.131 AC: 4294 AN: 32800

South Asian (SAS) AF: 0.0661 AC: 4108 AN: 62110

European-Finnish (FIN) AF: 0.166 AC: 8306 AN: 49934

Middle Eastern (MID) AF: 0.128 AC: 647 AN: 5036

European-Non Finnish (NFE) AF: 0.141 AC: 132550 AN: 937786

Other (OTH) AF: 0.144 AC: 7235 AN: 50224

GnomAD4 genome AF: 0.175 AC: 26533 AN: 152042 Hom.: 2647 Cov.: 32 AF XY: 0.172 AC XY: 12816 AN XY: 74318

African (AFR) AF: 0.263 AC: 10897 AN: 41454

American (AMR) AF: 0.125 AC: 1917 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 741 AN: 3472

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5174

South Asian (SAS) AF: 0.0723 AC: 348 AN: 4814

European-Finnish (FIN) AF: 0.170 AC: 1793 AN: 10556

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9801 AN: 67980

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.156 Hom.: 452

Bravo AF: 0.174

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.62
PhyloP100		-2.4
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: rs10173081; hg19: chr2-102957348; COSMIC: COSV52113963; COSMIC: COSV52113963;