16-3067569-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001376923.1(IL32):c.70A>G(p.Arg24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,912 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (9 hom.)
• Consequence: IL32 NM_001376923.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004132837).
• BP6: Variant 16-3067569-A-G is Benign according to our data. Variant chr16-3067569-A-G is described in ClinVar as [Benign]. Clinvar id is 776966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00643 (978/152188) while in subpopulation AFR AF= 0.0207 (861/41504). AF 95% confidence interval is 0.0196. There are 10 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL32	NM_001376923.1	c.70A>G	p.Arg24Gly	missense_variant	4/7	ENST00000525643.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL32	ENST00000525643.7	c.70A>G	p.Arg24Gly	missense_variant	4/7	1	NM_001376923.1	A2

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 971 AN: 152070 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00255 AC: 640 AN: 251346 Hom.: 6 AF XY: 0.00247 AC XY: 336 AN XY: 135834

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00778

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00118 AC: 1727 AN: 1461724 Hom.: 9 Cov.: 33 AF XY: 0.00131 AC XY: 956 AN XY: 727160

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00723

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00643 AC: 978 AN: 152188 Hom.: 10 Cov.: 32 AF XY: 0.00610 AC XY: 454 AN XY: 74392

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00206 Hom.: 2

Bravo AF: 0.00680

ESP6500AA AF: 0.0180 AC: 79

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00336 AC: 408

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	0.010
Dann	Benign	0.73
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0056	N
MetaRNN	Benign	0.0041	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	-1.0	T
MutationTaster	Benign	1.0	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
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N;D;.;D;D;D;N;N;N;D;N;D;N;N;N;D;N;D;N;D;D;D;N;D;N
REVEL	Benign	0.12
Sift	Benign	0.16	T;T;.;T;D;T;T;T;T;D;T;T;T;T;T;T;T;T;T;D;T;T;T;D;T
Sift4G	Benign	0.087	T;T;D;D;T;D;T;T;T;T;T;T;T;T;T;T;T;D;T;T;D;T;T;D;T
Polyphen		0.18	B;B;B;.;B;B;B;B;B;B;B;B;B;B;B;B;.;B;B;B;.;B;B;.;.
Vest4		0.19
MVP		0.38
MPC		0.18
ClinPred		0.0038	T
GERP RS		-4.0
Varity_R		0.15
gMVP		0.011

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs144473418; hg19: chr16-3117570; COSMIC: COSV99051157; COSMIC: COSV99051157;