rs4988958

Variant names:

• chr2-102351825-T-C
• rs4988958
• NM_016232.5:c.1575T>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.1575T>C​(p.Ser525Ser) 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 1,612,504 control chromosomes in the GnomAD database, including 122,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.45 (17710 hom., cov: 30)
  • Exomes 𝑓: 0.37 (105029 hom.)
• Consequence: IL1RL1 NM_016232.5 synonymous
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.158
• Publications: 41 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=-0.82).
• BP7: Synonymous conserved (PhyloP=0.158 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.1575T>C	p.Ser525Ser	synonymous	Exon 11 of 11	NP_057316.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1575T>C	p.Ser525Ser	synonymous	Exon 11 of 11	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000908526.1		c.1575T>C	p.Ser525Ser	synonymous	Exon 12 of 12	ENSP00000578585.1
	IL1RL1	ENST00000908527.1		c.1575T>C	p.Ser525Ser	synonymous	Exon 11 of 11	ENSP00000578586.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68490 AN: 151754 Hom.: 17681 Cov.: 30

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.341 AC: 85650 AN: 251140 AF XY: 0.332

Gnomad AFR exome AF: 0.709

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.368 AC: 538094 AN: 1460630 Hom.: 105029 Cov.: 36 AF XY: 0.362 AC XY: 263069 AN XY: 726690

African (AFR) AF: 0.714 AC: 23877 AN: 33456

American (AMR) AF: 0.230 AC: 10269 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12244 AN: 26132

East Asian (EAS) AF: 0.150 AC: 5966 AN: 39660

South Asian (SAS) AF: 0.183 AC: 15814 AN: 86234

European-Finnish (FIN) AF: 0.415 AC: 22127 AN: 53382

Middle Eastern (MID) AF: 0.283 AC: 1632 AN: 5766

European-Non Finnish (NFE) AF: 0.381 AC: 423770 AN: 1110916

Other (OTH) AF: 0.371 AC: 22395 AN: 60364

GnomAD4 genome AF: 0.451 AC: 68570 AN: 151874 Hom.: 17710 Cov.: 30 AF XY: 0.444 AC XY: 32981 AN XY: 74230

African (AFR) AF: 0.702 AC: 29057 AN: 41412

American (AMR) AF: 0.318 AC: 4846 AN: 15254

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

East Asian (EAS) AF: 0.128 AC: 659 AN: 5162

South Asian (SAS) AF: 0.199 AC: 961 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4443 AN: 10542

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25650 AN: 67906

Other (OTH) AF: 0.409 AC: 859 AN: 2100

Alfa AF: 0.403 Hom.: 20889

Bravo AF: 0.458

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.380

EpiControl AF: 0.383

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	-0.82
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		0.16
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: rs4988958; hg19: chr2-102968285; COSMIC: COSV52113226; COSMIC: COSV52113226;