chr16-3067606-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001376923.1(IL32):c.107G>A(p.Arg36His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,610,386 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R36C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 20 hom. )

Consequence

IL32
NM_001376923.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

Publications

10 publications found

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]

IL32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044682026).

BP6

Variant 16-3067606-G-A is Benign according to our data. Variant chr16-3067606-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 710339.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL32	NM_001376923.1	MANE Select	c.107G>A	p.Arg36His	missense	Exon 4 of 7	NP_001363852.1	P24001-2
IL32	NM_001308078.4		c.245G>A	p.Arg82His	missense	Exon 3 of 6	NP_001295007.1	P24001-1
IL32	NM_001369587.3		c.245G>A	p.Arg82His	missense	Exon 3 of 6	NP_001356516.1	P24001-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL32	ENST00000525643.7	TSL:1 MANE Select	c.107G>A	p.Arg36His	missense	Exon 4 of 7	ENSP00000432218.3	P24001-2
IL32	ENST00000396890.6	TSL:1	c.245G>A	p.Arg82His	missense	Exon 3 of 6	ENSP00000380099.2	P24001-1
IL32	ENST00000325568.9	TSL:1	c.107G>A	p.Arg36His	missense	Exon 4 of 7	ENSP00000324742.5	P24001-2

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

598

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00565

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00371

AC:

928

AN:

250216

AF XY:

0.00382

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00398

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00765

Gnomad NFE exome

AF:

0.00528

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00389

AC:

5672

AN:

1458122

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2829

AN XY:

725620

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

33390

American (AMR)

AF:

0.000850

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

113

AN:

26116

East Asian (EAS)

AF:

0.000227

AC:

AN:

39680

South Asian (SAS)

AF:

0.00151

AC:

130

AN:

86174

European-Finnish (FIN)

AF:

0.00818

AC:

429

AN:

52452

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00425

AC:

4715

AN:

1109544

Other (OTH)

AF:

0.00272

AC:

164

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

292

583

875

1166

1458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00393

AC:

598

AN:

152264

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

41542

American (AMR)

AF:

0.00118

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00103

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00565

AC:

384

AN:

67986

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00413

Hom.:

Bravo

AF:

0.00294

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00414

AC:

503

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00332

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

1.1

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.016

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.59

M_CAP

Benign

0.016

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

REVEL

Benign

0.089

Sift

Benign

0.087

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.12

MVP

0.40

MPC

0.15

ClinPred

0.0035

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.0075

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over