chr16-3067576-A-T

Variant names:

• chr16-3067576-A-T
• NM_001376923.1:c.77A>T

Variant summary

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

The NM_001376923.1(IL32):​c.77A>T​(p.Tyr26Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: IL32 NM_001376923.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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=0.029108614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1	c.77A>T	p.Tyr26Phe	missense_variant	Exon 4 of 7	ENST00000525643.7	NP_001363852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL32	ENST00000525643.7	c.77A>T	p.Tyr26Phe	missense_variant	Exon 4 of 7	1	NM_001376923.1	ENSP00000432218.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

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: 8.99e-7

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	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.0030
DANN	Benign	0.17
DEOGEN2	Benign	0.0039	.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;T;.;.;.;.;T;T;.;T;.
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.53	.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;T;T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.029	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	-0.97	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;N;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.16	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	0.10
Sift	Benign	1.0	T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.70	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
Polyphen		0.0	B;B;B;.;B;B;B;B;B;B;B;B;B;B;B;B;.;B;B;B;.;B;B;.;.
Vest4		0.073
MutPred		0.32		.;Loss of phosphorylation at Y72 (P = 0.0654);.;.;.;.;.;.;.;.;.;Loss of phosphorylation at Y72 (P = 0.0654);.;.;.;Loss of phosphorylation at Y72 (P = 0.0654);.;Loss of phosphorylation at Y72 (P = 0.0654);.;.;.;Loss of phosphorylation at Y72 (P = 0.0654);.;Loss of phosphorylation at Y72 (P = 0.0654);.;
MVP		0.38
MPC		0.098
ClinPred		0.020	T
GERP RS		-4.0
Varity_R		0.10
gMVP		0.0064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr16-3117577;