2-102340744-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016232.5(IL1RL1):c.526G>A(p.Ala176Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,597,556 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (18 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069009066).
• BP6: Variant 2-102340744-G-A is Benign according to our data. Variant chr2-102340744-G-A is described in ClinVar as [Benign]. Clinvar id is 1629553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00307 (468/152338) while in subpopulation EAS AF= 0.0322 (167/5192). AF 95% confidence interval is 0.0282. There are 3 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.526G>A	p.Ala176Thr	missense_variant	5/11	ENST00000233954.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.526G>A	p.Ala176Thr	missense_variant	5/11	1	NM_016232.5	P1

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 468 AN: 152220 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00420 AC: 987 AN: 234962 Hom.: 10 AF XY: 0.00395 AC XY: 505 AN XY: 127756

Gnomad AFR exome AF: 0.00145

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0294

Gnomad SAS exome AF: 0.00242

Gnomad FIN exome AF: 0.000419

Gnomad NFE exome AF: 0.00212

Gnomad OTH exome AF: 0.00423

GnomAD4 exome AF: 0.00248 AC: 3579 AN: 1445218 Hom.: 18 Cov.: 30 AF XY: 0.00247 AC XY: 1775 AN XY: 719232

Gnomad4 AFR exome AF: 0.00264

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.0265

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.000450

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.00372

GnomAD4 genome AF: 0.00307 AC: 468 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00313 AC XY: 233 AN XY: 74494

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00364 Hom.: 6

Bravo AF: 0.00385

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00463 AC: 562

Asia WGS AF: 0.00808 AC: 29 AN: 3478

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

Feb 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.27
Dann	Benign	0.70
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.70	T;T;T;T
MetaRNN	Benign	0.0069	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.30	N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.28	T;T;T;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.14, 0.22	.;B;B;.
Vest4		0.082
MVP		0.19
MPC		0.011
ClinPred		0.0019	T
GERP RS		-4.0
Varity_R		0.11
gMVP		0.44

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: rs34225180; hg19: chr2-102957204; COSMIC: COSV52113312; COSMIC: COSV52113312;