2-102343318-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_016232.5(IL1RL1):c.873C>T(p.Asp291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,614,166 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (50 hom.)
• Consequence: IL1RL1 NM_016232.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.654

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-102343318-C-T is Benign according to our data. Variant chr2-102343318-C-T is described in ClinVar as [Benign]. Clinvar id is 767810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.654 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2087/152280) while in subpopulation AFR AF= 0.0471 (1958/41554). AF 95% confidence interval is 0.0454. There are 57 homozygotes in gnomad4. There are 969 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.873C>T	p.Asp291=	synonymous_variant	8/11	ENST00000233954.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.873C>T	p.Asp291=	synonymous_variant	8/11	1	NM_016232.5	P1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2071 AN: 152162 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00374 AC: 939 AN: 251174 Hom.: 19 AF XY: 0.00271 AC XY: 368 AN XY: 135726

Gnomad AFR exome AF: 0.0485

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00141 AC: 2060 AN: 1461886 Hom.: 50 Cov.: 33 AF XY: 0.00122 AC XY: 885 AN XY: 727244

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.00323

GnomAD4 genome AF: 0.0137 AC: 2087 AN: 152280 Hom.: 57 Cov.: 32 AF XY: 0.0130 AC XY: 969 AN XY: 74462

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00586 Hom.: 4

Bravo AF: 0.0164

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.22
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs35298562; hg19: chr2-102959778; COSMIC: COSV52112751; COSMIC: COSV52112751;