rs4988958

chr2-102351825-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016232.5(IL1RL1):c.1575T>C(p.Ser525=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.1575T>C	p.Ser525=	synonymous_variant	11/11	ENST00000233954.6
IL1RL1	XM_006712839.4	c.1575T>C	p.Ser525=	synonymous_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.1575T>C	p.Ser525=	synonymous_variant	11/11	1	NM_016232.5	P1
IL18R1	ENST00000410040.5	c.-28-10808T>C		intron_variant		2

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

GnomAD3 exomes AF: 0.341 AC: 85650 AN: 251140 Hom.: 17296 AF XY: 0.332 AC XY: 45038 AN XY: 135766

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 SAS exome AF: 0.179

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

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.371

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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.409

Alfa AF: 0.395 Hom.: 16054

Bravo AF: 0.458

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.380

EpiControl AF: 0.383

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.1
Dann	Benign	0.71

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: rs4988958; hg19: chr2-102968285; COSMIC: COSV52113226; COSMIC: COSV52113226;