chr2-102343750-T-A

Variant names:

• chr2-102343750-T-A
• rs3771175
• ENST00000427077.1:n.*695T>A

Variant summary

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

The ENST00000427077.1(IL1RL1):​n.*695T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,207,844 control chromosomes in the GnomAD database, including 13,524 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 0.18 (2687 hom., cov: 33)
  • Exomes 𝑓: 0.14 (10837 hom.)
• Consequence: IL1RL1 ENST00000427077.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 45 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427077.1. 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+335T>A		intron	N/A	NP_057316.3
	IL1RL1	NR_104167.2		n.1705T>A		non_coding_transcript_exon	Exon 9 of 9
	IL1RL1	NM_003856.4		c.*318T>A		3_prime_UTR	Exon 8 of 8	NP_003847.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000427077.1	TSL:1	n.*695T>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000391120.1
	IL1RL1	ENST00000311734.6	TSL:1	c.*318T>A		3_prime_UTR	Exon 8 of 8	ENSP00000310371.2
	IL1RL1	ENST00000427077.1	TSL:1	n.*695T>A		3_prime_UTR	Exon 9 of 9	ENSP00000391120.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26656 AN: 152108 Hom.: 2681 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.140 AC: 147585 AN: 1055620 Hom.: 10837 Cov.: 32 AF XY: 0.139 AC XY: 69328 AN XY: 500148

African (AFR) AF: 0.276 AC: 6616 AN: 24004

American (AMR) AF: 0.101 AC: 1164 AN: 11472

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 2721 AN: 12038

East Asian (EAS) AF: 0.107 AC: 2085 AN: 19446

South Asian (SAS) AF: 0.0638 AC: 2434 AN: 38122

European-Finnish (FIN) AF: 0.163 AC: 1862 AN: 11416

Middle Eastern (MID) AF: 0.117 AC: 304 AN: 2590

European-Non Finnish (NFE) AF: 0.139 AC: 124650 AN: 895978

Other (OTH) AF: 0.142 AC: 5749 AN: 40554

GnomAD4 genome AF: 0.175 AC: 26686 AN: 152224 Hom.: 2687 Cov.: 33 AF XY: 0.174 AC XY: 12925 AN XY: 74438

African (AFR) AF: 0.264 AC: 10949 AN: 41510

American (AMR) AF: 0.126 AC: 1925 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3472

East Asian (EAS) AF: 0.0920 AC: 476 AN: 5176

South Asian (SAS) AF: 0.0723 AC: 349 AN: 4830

European-Finnish (FIN) AF: 0.177 AC: 1882 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9817 AN: 68010

Other (OTH) AF: 0.171 AC: 361 AN: 2112

Alfa AF: 0.163 Hom.: 291

Bravo AF: 0.174

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.54
PhyloP100		-1.3
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: rs3771175; hg19: chr2-102960210; COSMIC: COSV52113973; COSMIC: COSV52113973;