dbSNP rs372880215: IL36RN:p.Thr77Asn (chr2-113062238-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T77I) has been classified as Uncertain significance.

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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

psoriasis 14, pustular
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
pustulosis palmaris et plantaris
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IL36RN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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 rank	MANE	Protein
IL36RN	NM_012275.3 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 4 of 5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 4 of 5		NP_775262.1
IL36RN	XM_047443918.1 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 5 of 6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
IL36RN	ENST00000393200.7 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 4 of 5	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 4 of 5	1		ENSP00000259212.3
IL36RN	ENST00000437409.2 link	c.230C>A	p.Thr77Asn	missense_variant	Exon 3 of 4	1		ENSP00000409262.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251286

AF XY:

0.00000736

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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;.

PhyloP100

0.14

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

PromoterAI

-0.0028

Neutral

(source)

Varity_R

0.16

gMVP

0.69

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over