16-3067576-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001376923.1(IL32):c.77A>G(p.Tyr26Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,613,838 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 9 hom. )

Consequence

IL32
NM_001376923.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.38

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004234284).

BP6

Variant 16-3067576-A-G is Benign according to our data. Variant chr16-3067576-A-G is described in ClinVar as [Benign]. Clinvar id is 776967.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 = 0.00643 (978/152176) while in subpopulation AFR AF= 0.0207 (861/41502). AF 95% confidence interval is 0.0196. There are 9 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 GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1 link	c.77A>G	p.Tyr26Cys	missense_variant	Exon 4 of 7	ENST00000525643.7	NP_001363852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL32	ENST00000525643.7 link	c.77A>G	p.Tyr26Cys	missense_variant	Exon 4 of 7	1	NM_001376923.1	ENSP00000432218.3		P24001-2

Frequencies

GnomAD3 genomes

AF:

0.00639

AC:

971

AN:

152058

Hom.:

Cov.:

show subpopulations

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:

0.00704

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00251

AC:

630

AN:

251278

Hom.:

AF XY:

0.00246

AC XY:

334

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00746

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00118

AC:

1719

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

952

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0202

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00709

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00643

AC:

978

AN:

152176

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

454

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0207

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00681

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00338

AC:

411

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

0.0020

DANN

Benign

0.20

DEOGEN2

Benign

0.0014

.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;T;.;.;.;.;T;T;.;T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.48

.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;T;T;T;T;T;T

MetaRNN

Benign

0.0042

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

MutationAssessor

Benign

0.0

.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;N;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

2.1

N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.088

T;T;.;T;D;T;T;T;T;D;T;T;T;T;T;T;T;T;T;D;T;T;T;T;T

Sift4G

Benign

0.17

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

0.0

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

Vest4

0.085

MVP

0.39

MPC

0.13

ClinPred

0.0049

GERP RS

-4.0

Varity_R

0.086

gMVP

0.0074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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