2-102345469-C-T

Variant names:

• chr2-102345469-C-T
• rs1946131
• ENST00000311734.6:c.*2037C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000311734.6(IL1RL1):​c.*2037C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 985,002 control chromosomes in the GnomAD database, including 5,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (978 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4295 hom.)
• Consequence: IL1RL1 ENST00000311734.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 21 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000311734.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.970+2054C>T		intron	N/A	NP_057316.3
	IL1RL1	NR_104167.2		n.3424C>T		non_coding_transcript_exon	Exon 9 of 9
	IL1RL1	NM_003856.4		c.*2037C>T		3_prime_UTR	Exon 8 of 8	NP_003847.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000311734.6	TSL:1	c.*2037C>T		3_prime_UTR	Exon 8 of 8	ENSP00000310371.2
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.970+2054C>T		intron	N/A	ENSP00000233954.1
	IL1RL1	ENST00000404917.6	TSL:2	c.*2037C>T		3_prime_UTR	Exon 7 of 7	ENSP00000384822.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16641 AN: 152046 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.101 AC: 84089 AN: 832840 Hom.: 4295 Cov.: 31 AF XY: 0.101 AC XY: 38960 AN XY: 384590

African (AFR) AF: 0.124 AC: 1949 AN: 15778

American (AMR) AF: 0.0803 AC: 79 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 787 AN: 5150

East Asian (EAS) AF: 0.0485 AC: 176 AN: 3630

South Asian (SAS) AF: 0.0916 AC: 1508 AN: 16460

European-Finnish (FIN) AF: 0.124 AC: 34 AN: 274

Middle Eastern (MID) AF: 0.260 AC: 421 AN: 1620

European-Non Finnish (NFE) AF: 0.0999 AC: 76120 AN: 761656

Other (OTH) AF: 0.110 AC: 3015 AN: 27288

GnomAD4 genome AF: 0.110 AC: 16662 AN: 152162 Hom.: 978 Cov.: 32 AF XY: 0.110 AC XY: 8196 AN XY: 74400

African (AFR) AF: 0.122 AC: 5041 AN: 41488

American (AMR) AF: 0.0996 AC: 1523 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3470

East Asian (EAS) AF: 0.0414 AC: 215 AN: 5188

South Asian (SAS) AF: 0.0825 AC: 398 AN: 4822

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10582

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7232 AN: 68012

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.105 Hom.: 751

Bravo AF: 0.108

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		0.092
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: rs1946131; hg19: chr2-102961929;