2-102351615-T-C

Variant names:

• chr2-102351615-T-C
• rs4988957
• NM_016232.5:c.1365T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016232.5(IL1RL1):​c.1365T>C​(p.Asn455Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,613,674 control chromosomes in the GnomAD database, including 122,805 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 0.45 (17753 hom., cov: 31)
  • Exomes 𝑓: 0.37 (105052 hom.)
• Consequence: IL1RL1 NM_016232.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 40 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=0.201 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.1365T>C	p.Asn455Asn	synonymous	Exon 11 of 11	NP_057316.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1365T>C	p.Asn455Asn	synonymous	Exon 11 of 11	ENSP00000233954.1
	IL18R1	ENST00000410040.5	TSL:2	c.-28-11018T>C		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68602 AN: 151876 Hom.: 17724 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.341 AC: 85769 AN: 251318 AF XY: 0.332

Gnomad AFR exome AF: 0.710

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.368 AC: 538625 AN: 1461680 Hom.: 105052 Cov.: 39 AF XY: 0.362 AC XY: 263295 AN XY: 727144

African (AFR) AF: 0.714 AC: 23885 AN: 33474

American (AMR) AF: 0.230 AC: 10271 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12246 AN: 26136

East Asian (EAS) AF: 0.151 AC: 5977 AN: 39672

South Asian (SAS) AF: 0.183 AC: 15823 AN: 86256

European-Finnish (FIN) AF: 0.414 AC: 22136 AN: 53412

Middle Eastern (MID) AF: 0.283 AC: 1633 AN: 5768

European-Non Finnish (NFE) AF: 0.382 AC: 424246 AN: 1111852

Other (OTH) AF: 0.371 AC: 22408 AN: 60390

GnomAD4 genome AF: 0.452 AC: 68681 AN: 151994 Hom.: 17753 Cov.: 31 AF XY: 0.445 AC XY: 33039 AN XY: 74274

African (AFR) AF: 0.702 AC: 29110 AN: 41454

American (AMR) AF: 0.318 AC: 4853 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3472

East Asian (EAS) AF: 0.128 AC: 664 AN: 5174

South Asian (SAS) AF: 0.199 AC: 959 AN: 4814

European-Finnish (FIN) AF: 0.423 AC: 4462 AN: 10550

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25669 AN: 67942

Other (OTH) AF: 0.412 AC: 868 AN: 2108

Alfa AF: 0.390 Hom.: 18284

Bravo AF: 0.457

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.380

EpiControl AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.32
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4988957; hg19: chr2-102968075; COSMIC: COSV52112924; COSMIC: COSV52112924;