rs1530551

Positions:

• chr2-113059989-T-C
• chr2-113059989-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012275.3(IL36RN):​c.29+522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,082 control chromosomes in the GnomAD database, including 36,753 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 0.69 (36753 hom., cov: 32)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579

Genes affected

IL36RN (HGNC:15561): (interleukin 36 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine was shown to specifically inhibit the activation of NF-kappaB induced by interleukin 1 family, member 6 (IL1F6). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.29+522T>C		intron_variant		ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.29+522T>C		intron_variant			NP_775262.1
IL36RN	XM_047443918.1	c.29+522T>C		intron_variant			XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.29+522T>C		intron_variant		1	NM_012275.3	ENSP00000376896	P1
IL36RN	ENST00000346807.7	c.29+522T>C		intron_variant		1		ENSP00000259212	P1
IL36RN	ENST00000437409.2	c.29+522T>C		intron_variant		1		ENSP00000409262	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104488 AN: 151964 Hom.: 36700 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.688 AC: 104593 AN: 152082 Hom.: 36753 Cov.: 32 AF XY: 0.693 AC XY: 51503 AN XY: 74334

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.711

Alfa AF: 0.630 Hom.: 45975

Bravo AF: 0.696

Asia WGS AF: 0.913 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1530551; hg19: chr2-113817566;