Variant rs144478519 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_012275.3(IL36RN):c.338C>A(p.Ser113Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

IL36RN
NM_012275.3 stop_gained

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.79

Variant links:

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]

IL36RN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.278 CDS is truncated, and there are 3 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-113062547-C-A is Pathogenic according to our data. Variant chr2-113062547-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2579641.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL36RN	NM_012275.3 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	5/5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	5/5		NP_775262.1
IL36RN	XM_047443918.1 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	6/6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IL36RN	ENST00000393200.7 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	5/5	1	NM_012275.3	ENSP00000376896	P1
IL36RN	ENST00000346807.7 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	5/5	1		ENSP00000259212	P1
IL36RN	ENST00000437409.2 linkuse as main transcript	c.338C>A	p.Ser113Ter	stop_gained	4/4	1		ENSP00000409262	P1
IL36RN	ENST00000514072.1 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/2	3		ENSP00000475308

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251204

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acrodermatitis continua suppurativa of Hallopeau

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Department of Human Genetics, Hannover Medical School

Sep 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.60

BayesDel_noAF

Pathogenic

0.55

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

MutationTaster

Benign

1.0

D;D

Vest4

0.55

GERP RS

4.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over