Variant 16-3068238-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001376923.1(IL32):c.200C>T(p.Pro67Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,593,120 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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 (★). Synonymous variant affecting the same amino acid position (i.e. P67P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 19 hom. )

Consequence

IL32
NM_001376923.1 missense, splice_region

Scores

Splicing: ADA: 0.0001899

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006112784).

BP6

Variant 16-3068238-C-T is Benign according to our data. Variant chr16-3068238-C-T is described in ClinVar as [Benign]. Clinvar id is 773304.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL32	NM_001376923.1 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant, splice_region_variant	6/7	ENST00000525643.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL32	ENST00000525643.7 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant, splice_region_variant	6/7	1	NM_001376923.1	A2	P24001-2

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00368

AC:

784

AN:

213332

Hom.:

AF XY:

0.00382

AC XY:

438

AN XY:

114664

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00328

Gnomad ASJ exome

AF:

0.00915

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.00196

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00664

GnomAD4 exome

AF:

0.00360

AC:

5188

AN:

1440842

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2590

AN XY:

714718

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00299

Gnomad4 ASJ exome

AF:

0.00952

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00334

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00451

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152278

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.00289

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00324

AC:

392

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.12

DANN

Benign

0.36

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0022

MetaRNN

Benign

0.0058

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;T;T

MetaSVM

Benign

-1.1

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

Uncertain

0.55

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;N;N;D;D;D;D;D;D;D;N;N

REVEL

Benign

0.089

Sift

Uncertain

0.0070

D;D;D;D;D;D;D;D;D;D;D;T;D;D;T;D;T;D;D;D;D;D;D;D;T;D;D

Sift4G

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;T;T;T

Polyphen

0.0020

B;B;.;B;B;B;B;B;B;.;B;.;B;B;.;B;.;.;.;B;B;.;B;B;.;.;.

Vest4

0.090

MVP

0.37

MPC

0.11

ClinPred

0.017

GERP RS

-3.8

Varity_R

0.036

gMVP

0.0040

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over