rs749087744

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014438.5(IL36B):​c.464G>C​(p.Arg155Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,576 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R155Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

IL36B
NM_014438.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804
Variant links:
Genes affected
IL36B (HGNC:15564): (interleukin 36 beta) The protein encoded by this gene is a member of the interleukin 1 cytokine family. Protein structure modeling indicated that this cytokine may contain a 12-stranded beta-trefoil structure that is conserved between IL1A (IL-A alpha) and IL1B (IL-1 beta). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.048342466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL36BNM_014438.5 linkc.464G>C p.Arg155Pro missense_variant Exon 6 of 6 ENST00000259213.9 NP_055253.2 Q9NZH7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL36BENST00000259213.9 linkc.464G>C p.Arg155Pro missense_variant Exon 6 of 6 1 NM_014438.5 ENSP00000259213.4 Q9NZH7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459576
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
726226
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.2
DANN
Benign
0.45
DEOGEN2
Benign
0.0029
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.00090
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.045
Sift
Benign
0.26
T
Sift4G
Benign
0.17
T
Polyphen
0.0080
B
Vest4
0.18
MutPred
0.25
Loss of MoRF binding (P = 5e-04);
MVP
0.014
MPC
0.076
ClinPred
0.20
T
GERP RS
-1.1
Varity_R
0.17
gMVP
0.083

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113780282; API