16-3067377-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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, single submitter B:1
• Conservation: PhyloP100: -4.43

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL32	NM_001376923.1	c.16G>A	p.Val6Ile	missense_variant, splice_region_variant	3/7	ENST00000525643.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL32	ENST00000525643.7	c.16G>A	p.Val6Ile	missense_variant, splice_region_variant	3/7	1	NM_001376923.1	A2

Frequencies

GnomAD3 genomes AF: 0.00730 AC: 1105 AN: 151426 Hom.: 13 Cov.: 32

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.: 4 AF XY: 0.00168 AC XY: 175 AN XY: 104342

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.: 13 Cov.: 32 AF XY: 0.000599 AC XY: 409 AN XY: 683060

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.: 17 Cov.: 32 AF XY: 0.00705 AC XY: 522 AN XY: 74008

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.: 1

Bravo AF: 0.00870

ESP6500AA AF: 0.0287 AC: 126

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00234 AC: 284

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.0020
Dann	Benign	0.80
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00027	N
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	T
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
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	Benign	0.47	T
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
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	T
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

Other links and lift over

dbSNP: rs114354531; hg19: chr16-3117378; COSMIC: COSV50404348; COSMIC: COSV50404348;