rs3771188

Variant names:

• chr2-102223888-T-C
• rs3771188
• NM_003854.4:c.992-2010T>C

Variant summary

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

The NM_003854.4(IL1RL2):​c.992-2010T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,094 control chromosomes in the GnomAD database, including 2,382 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 0.16 (2382 hom., cov: 32)
• Consequence: IL1RL2 NM_003854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 4 publications found

Genes affected

IL1RL2 (HGNC:5999): (interleukin 1 receptor like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. An experiment with transient gene expression demonstrated that this receptor was incapable of binding to interleukin 1 alpha and interleukin 1 beta with high affinity. This gene and four other interleukin 1 receptor family genes, including interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 1 (IL1RL1), and interleukin 18 receptor 1 (IL18R1), form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL2	NM_003854.4	c.992-2010T>C		intron_variant	Intron 8 of 11	ENST00000264257.7	NP_003845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL2	ENST00000264257.7	c.992-2010T>C		intron_variant	Intron 8 of 11	1	NM_003854.4	ENSP00000264257.2
IL1RL2	ENST00000441515.3	c.638-2010T>C		intron_variant	Intron 6 of 9	1		ENSP00000413348.2
IL1RL2	ENST00000481806.1	n.654-2010T>C		intron_variant	Intron 6 of 9	5

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24172 AN: 151976 Hom.: 2370 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24215 AN: 152094 Hom.: 2382 Cov.: 32 AF XY: 0.159 AC XY: 11846 AN XY: 74358

African (AFR) AF: 0.193 AC: 7989 AN: 41472

American (AMR) AF: 0.293 AC: 4469 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1159 AN: 5180

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1370 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8279 AN: 67986

Other (OTH) AF: 0.150 AC: 316 AN: 2106

Alfa AF: 0.138 Hom.: 7392

Bravo AF: 0.179

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.29
PhyloP100		-0.12
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: rs3771188; hg19: chr2-102840348;