2-102338283-G-T

Position:

• chr2-102338283-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016232.5(IL1RL1):​c.19G>T​(p.Ala7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,606,812 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25

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]

IL1RL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038966238).
• BP6: Variant 2-102338283-G-T is Benign according to our data. Variant chr2-102338283-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 781683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.19G>T	p.Ala7Ser	missense_variant	2/11	ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.19G>T	p.Ala7Ser	missense_variant	2/11	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 152098 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00115 AC: 288 AN: 249596 Hom.: 1 AF XY: 0.000837 AC XY: 113 AN XY: 134948

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00771

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00329

GnomAD4 exome AF: 0.000311 AC: 452 AN: 1454596 Hom.: 1 Cov.: 27 AF XY: 0.000245 AC XY: 177 AN XY: 723818

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.00817

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000634

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.000865

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152216 Hom.: 3 Cov.: 33 AF XY: 0.00120 AC XY: 89 AN XY: 74420

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000125 Hom.: 2

Bravo AF: 0.00283

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000700 AC: 85

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T;T;.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.54	T;T;T;T
MetaRNN	Benign	0.0039	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.81	L;.;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.82	N;D;N;N
REVEL	Benign	0.056
Sift	Benign	0.030	D;D;D;D
Sift4G	Benign	0.39	T;T;D;D
Polyphen		0.48	P;.;P;.
Vest4		0.11
MVP		0.70
MPC		0.026
ClinPred		0.022	T
GERP RS		3.3
Varity_R		0.052
gMVP		0.47

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: rs142516188; hg19: chr2-102954743;