2-102016112-A-G

Variant names:

• chr2-102016112-A-G
• rs3819370
• NM_004633.4:c.513+61A>G

Variant summary

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

The NM_004633.4(IL1R2):​c.513+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,323,420 control chromosomes in the GnomAD database, including 14,520 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 0.17 (2607 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11913 hom.)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 8 publications found

Genes affected

IL1R2 (HGNC:5994): (interleukin 1 receptor type 2) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004633.4. 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
	IL1R2	NM_004633.4	MANE Select	c.513+61A>G		intron	N/A	NP_004624.1
	IL1R2	NM_001261419.2		c.513+61A>G		intron	N/A	NP_001248348.1
	IL1R2	NR_048564.2		n.730+61A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.513+61A>G		intron	N/A	ENSP00000330959.3
	IL1R2	ENST00000393414.6	TSL:1	c.513+61A>G		intron	N/A	ENSP00000377066.2
	IL1R2	ENST00000441002.1	TSL:1	c.513+61A>G		intron	N/A	ENSP00000414611.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25734 AN: 152016 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.128 AC: 150210 AN: 1171286 Hom.: 11913 Cov.: 14 AF XY: 0.130 AC XY: 76596 AN XY: 588628

African (AFR) AF: 0.271 AC: 7284 AN: 26860

American (AMR) AF: 0.181 AC: 6675 AN: 36974

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2815 AN: 23086

East Asian (EAS) AF: 0.316 AC: 11474 AN: 36284

South Asian (SAS) AF: 0.205 AC: 15084 AN: 73626

European-Finnish (FIN) AF: 0.182 AC: 9145 AN: 50218

Middle Eastern (MID) AF: 0.167 AC: 858 AN: 5138

European-Non Finnish (NFE) AF: 0.103 AC: 89578 AN: 869120

Other (OTH) AF: 0.146 AC: 7297 AN: 49980

GnomAD4 genome AF: 0.169 AC: 25775 AN: 152134 Hom.: 2607 Cov.: 32 AF XY: 0.173 AC XY: 12893 AN XY: 74372

African (AFR) AF: 0.266 AC: 11030 AN: 41474

American (AMR) AF: 0.156 AC: 2386 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1482 AN: 5180

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4814

European-Finnish (FIN) AF: 0.172 AC: 1815 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7183 AN: 68020

Other (OTH) AF: 0.151 AC: 319 AN: 2116

Alfa AF: 0.149 Hom.: 267

Bravo AF: 0.173

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3819370; hg19: chr2-102632574; COSMIC: COSV60206795;