16-3067377-G-C

Variant names:

• chr16-3067377-G-C
• rs114354531
• NM_001376923.1:c.16G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376923.1(IL32):​c.16G>C​(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 𝑓: 7.2e-7 (0 hom.)
• Consequence: IL32 NM_001376923.1 missense, splice_region
• Scores: Splicing: ADA: 0.0005954
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43

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]

ACMG classification

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
IL32	NM_001376923.1	c.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
IL32	ENST00000525643.7	c.16G>C	p.Val6Leu	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_001376923.1	ENSP00000432218.3

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

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

Other links and lift over

dbSNP: rs114354531; hg19: chr16-3117378;