16-3067377-G-C

Variant summary

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

The NM_001376923.1(IL32):ā€‹c.16G>Cā€‹(p.Val6Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

IL32
NM_001376923.1 missense, splice_region

Scores

19
Splicing: ADA: 0.0005954
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.43
Variant links:
Genes affected
IL32 (HGNC:16830): (interleukin 32) This gene encodes a member of the cytokine family. The protein contains a tyrosine sulfation site, 3 potential N-myristoylation sites, multiple putative phosphorylation sites, and an RGD cell-attachment sequence. Expression of this protein is increased after the activation of T-cells by mitogens or the activation of NK cells by IL-2. This protein induces the production of TNFalpha from macrophage cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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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=0.05121389).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL32NM_001376923.1 linkc.16G>C p.Val6Leu missense_variant, splice_region_variant Exon 3 of 7 ENST00000525643.7 NP_001363852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL32ENST00000525643.7 linkc.16G>C p.Val6Leu missense_variant, splice_region_variant Exon 3 of 7 1 NM_001376923.1 ENSP00000432218.3 P24001-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.21e-7
AC:
1
AN:
1386994
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
683060
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:
9.31e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
0.0070
DANN
Benign
0.73
DEOGEN2
Benign
0.010
.;T;T;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;T;.;.
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.0024
N
LIST_S2
Benign
0.41
.;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;T;.;T;T;T;T;T;T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.051
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N;.;N;.;N;N;N;N;N;.;N;N;N;N;N;N;.;N;.;N;N;N;N;N;.;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.98
N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.031
Sift
Benign
0.39
T;D;.;T;T;T;T;T;T;T;D;T;T;T;T;T;D;D;T;D;T;T;D;T;T;D;T;D
Sift4G
Benign
0.57
.;T;D;.;D;.;.;.;.;.;T;.;D;.;.;D;T;T;D;T;.;.;T;.;D;T;D;D
Polyphen
0.0020
B;B;B;B;B;B;B;B;B;B;B;B;.;B;B;.;B;.;.;B;B;B;B;B;.;.;.;.
Vest4
0.12
MutPred
0.21
Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);Loss of MoRF binding (P = 0.0831);
MVP
0.39
MPC
0.29
ClinPred
0.033
T
GERP RS
-3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.0029

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00060
dbscSNV1_RF
Benign
0.13
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.

Other links and lift over

dbSNP: rs114354531; hg19: chr16-3117378; API