chr16-3067377-G-A

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.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. 17/22 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 (★★).

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

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1 link	c.16G>A	p.Val6Ile	missense_variant, splice_region_variant	Exon 3 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.16G>A	p.Val6Ile	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_001376923.1	ENSP00000432218.3		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

GnomAD3 exomes

AF:

0.00231

AC:

454

AN:

196390

Hom.:

AF XY:

0.00168

AC XY:

175

AN XY:

104342

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 SAS exome

AF:

0.000108

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

Gnomad4 AFR exome

AF:

0.0249

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.0000403

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000382

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00739

AC:

1120

AN:

151544

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

522

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00571

Alfa

AF:

0.000870

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

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

- -

Jul 21, 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

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.0020

DANN

Benign

0.80

DEOGEN2

Benign

0.0061

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

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.39

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

MetaRNN

Benign

0.0028

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;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

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

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.54

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;N

REVEL

Benign

0.017

Sift

Benign

0.24

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

Sift4G

Benign

0.60

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

Polyphen

0.054

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

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

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

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