dbSNP rs114354531: IL32:p.Val6Ile (chr16-3067377-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001376923.1(IL32):c.16G>A(p.Val6Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,538,538 control chromosomes in the GnomAD database, including 30 homozygotes. 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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 13 hom. )

Consequence

IL32
NM_001376923.1 missense, splice_region

Scores

Splicing: ADA: 0.0001971

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.43

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027642846).

BP6

Variant 16-3067377-G-A is Benign according to our data. Variant chr16-3067377-G-A is described in ClinVar as Benign. ClinVar VariationId is 786636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00739 (1120/151544) while in subpopulation AFR AF = 0.0258 (1065/41296). AF 95% confidence interval is 0.0245. There are 17 homozygotes in GnomAd4. There are 522 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 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.16G>A	p.Val6Ile	missense splice_region	Exon 3 of 7	NP_001363852.1	P24001-2
IL32	NM_001308078.4		c.16G>A	p.Val6Ile	missense splice_region	Exon 3 of 6	NP_001295007.1	P24001-1
IL32	NM_001369587.3		c.16G>A	p.Val6Ile	missense splice_region	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.16G>A	p.Val6Ile	missense splice_region	Exon 3 of 7	ENSP00000432218.3	P24001-2
IL32	ENST00000396890.6	TSL:1	c.16G>A	p.Val6Ile	missense splice_region	Exon 3 of 6	ENSP00000380099.2	P24001-1
IL32	ENST00000325568.9	TSL:1	c.16G>A	p.Val6Ile	missense splice_region	Exon 3 of 7	ENSP00000324742.5	P24001-2

Frequencies

GnomAD3 genomes

AF:

0.00730

AC:

1105

AN:

151426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00577

GnomAD2 exomes

AF:

0.00231

AC:

454

AN:

196390

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000643

Gnomad OTH exome

AF:

0.000219

GnomAD4 exome

AF:

0.000678

AC:

940

AN:

1386994

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

409

AN XY:

683060

show subpopulations

African (AFR)

AF:

0.0249

AC:

768

AN:

30898

American (AMR)

AF:

0.00125

AC:

AN:

33484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21290

East Asian (EAS)

AF:

0.0000512

AC:

AN:

39050

South Asian (SAS)

AF:

0.0000403

AC:

AN:

74440

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50718

Middle Eastern (MID)

AF:

0.00129

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.0000382

AC:

AN:

1074600

Other (OTH)

AF:

0.00133

AC:

AN:

57106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00739

AC:

1120

AN:

151544

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

522

AN XY:

74008

show subpopulations

African (AFR)

AF:

0.0258

AC:

1065

AN:

41296

American (AMR)

AF:

0.00262

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10396

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67926

Other (OTH)

AF:

0.00571

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00269

Hom.:

Bravo

AF:

0.00870

ESP6500AA

AF:

0.0287

AC:

126

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00234

AC:

284

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.0020

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-4.4

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.54

REVEL

Benign

0.017

Sift

Benign

0.24

Sift4G

Benign

0.60

Polyphen

0.054

Vest4

0.055

MVP

0.40

MPC

0.26

ClinPred

0.0034

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.0022

Mutation Taster

=295/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.064

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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