Variant chr2-113062238-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_012275.3(IL36RN):c.230C>A(p.Thr77Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL36RN
NM_012275.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143

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 Uncertain_significance. Variant got 3 ACMG points.

PM1

In a disulfide_bond (size 146) in uniprot entity I36RA_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_012275.3

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34530777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL36RN	NM_012275.3 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	4/5	ENST00000393200.7	NP_036407.1	Q9UBH0A0A024R518
IL36RN	NM_173170.1 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	4/5		NP_775262.1	Q9UBH0A0A024R518
IL36RN	XM_047443918.1 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	5/6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL36RN	ENST00000393200.7 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	4/5	1	NM_012275.3	ENSP00000376896.2	Q9UBH0
IL36RN	ENST00000346807.7 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	4/5	1		ENSP00000259212.3	Q9UBH0
IL36RN	ENST00000437409.2 linkuse as main transcript	c.230C>A	p.Thr77Asn	missense_variant	3/4	1		ENSP00000409262.2	Q9UBH0C9JTH1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251286

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135816

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:

0.00000137

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.9

DANN

Benign

0.60

DEOGEN2

Benign

0.32

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.55

.;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

3.1

M;M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.80

P;P;.

Vest4

0.37

MutPred

0.51

Loss of glycosylation at T77 (P = 0.0835);Loss of glycosylation at T77 (P = 0.0835);Loss of glycosylation at T77 (P = 0.0835);

MVP

0.73

MPC

0.33

ClinPred

0.16

GERP RS

1.9

Varity_R

0.16

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over