NM_004633.4:c.-62+6806T>G

Variant names:

• chr2-101998817-T-G
• rs2071008
• NM_004633.4:c.-62+6806T>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.-62+6806T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,066 control chromosomes in the GnomAD database, including 31,531 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 0.63 (31531 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.-62+6806T>G		intron_variant	Intron 1 of 8	ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.-62+6806T>G		intron_variant	Intron 1 of 8	1	NM_004633.4	ENSP00000330959.3
IL1R2	ENST00000464994.5	n.74+6784T>G		intron_variant	Intron 1 of 2	3
IL1R2	ENST00000493749.1	n.52+6806T>G		intron_variant	Intron 1 of 2	2
IL1R2	ENST00000393414.6	c.-361T>G		upstream_gene_variant		1		ENSP00000377066.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95710 AN: 151948 Hom.: 31474 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.630 AC: 95827 AN: 152066 Hom.: 31531 Cov.: 32 AF XY: 0.641 AC XY: 47653 AN XY: 74334

African (AFR) AF: 0.805 AC: 33397 AN: 41484

American (AMR) AF: 0.615 AC: 9396 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4015 AN: 5168

South Asian (SAS) AF: 0.646 AC: 3116 AN: 4826

European-Finnish (FIN) AF: 0.724 AC: 7659 AN: 10582

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34657 AN: 67944

Other (OTH) AF: 0.596 AC: 1257 AN: 2110

Alfa AF: 0.519 Hom.: 9202

Bravo AF: 0.632

Asia WGS AF: 0.754 AC: 2624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.63
DANN	Benign	0.19
PhyloP100		-0.42
PromoterAI		-0.0085	Neutral
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: rs2071008; hg19: chr2-102615279;