16-3067377-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376923.1(IL32):​c.16G>T​(p.Val6Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,386,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V6I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: IL32 NM_001376923.1 missense, splice_region
• Scores: Splicing: ADA: 0.005674
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058654666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376923.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	NM_001376923.1	MANE Select	c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 7	NP_001363852.1	P24001-2
	IL32	NM_001308078.4		c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 6	NP_001295007.1	P24001-1
	IL32	NM_001369587.3		c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 6	NP_001356516.1	P24001-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	ENST00000525643.7	TSL:1 MANE Select	c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 7	ENSP00000432218.3	P24001-2
	IL32	ENST00000396890.6	TSL:1	c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 6	ENSP00000380099.2	P24001-1
	IL32	ENST00000325568.9	TSL:1	c.16G>T	p.Val6Phe	missense splice_region	Exon 3 of 7	ENSP00000324742.5	P24001-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000509 AC: 1 AN: 196390 AF XY: 0.00000958

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: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 19 AN: 1386994 Hom.: 0 Cov.: 32 AF XY: 0.0000132 AC XY: 9 AN XY: 683060

African (AFR) AF: 0.00 AC: 0 AN: 30898

American (AMR) AF: 0.00 AC: 0 AN: 33484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21290

East Asian (EAS) AF: 0.00 AC: 0 AN: 39050

South Asian (SAS) AF: 0.00 AC: 0 AN: 74440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.0000158 AC: 17 AN: 1074600

Other (OTH) AF: 0.0000350 AC: 2 AN: 57106

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.3
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.080
Sift	Benign	0.17	T
Sift4G	Benign	0.25	T
Polyphen		0.39	B
Vest4		0.14
MutPred		0.23		Loss of MoRF binding (P = 0.0753)
MVP		0.29
MPC		0.52
ClinPred		0.071	T
GERP RS		-3.8
Varity_R		0.19
gMVP		0.0054
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0057
dbscSNV1_RF	Benign	0.20
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

Other links and lift over

dbSNP: rs114354531; hg19: chr16-3117378;