16-3068239-A-G

Variant names:

• chr16-3068239-A-G
• rs140322567
• NM_001376923.1:c.201A>G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001376923.1(IL32):​c.201A>G​(p.Pro67Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,592,332 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts 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 0.0031 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (17 hom.)
• Consequence: IL32 NM_001376923.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.00008440
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.381

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-3068239-A-G is Benign according to our data. Variant chr16-3068239-A-G is described in ClinVar as [Benign]. Clinvar id is 710340.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.381 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1	c.201A>G	p.Pro67Pro	splice_region_variant, synonymous_variant	Exon 6 of 7	ENST00000525643.7	NP_001363852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL32	ENST00000525643.7	c.201A>G	p.Pro67Pro	splice_region_variant, synonymous_variant	Exon 6 of 7	1	NM_001376923.1	ENSP00000432218.3

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 468 AN: 152158 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00479

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00280 AC: 594 AN: 211768 Hom.: 3 AF XY: 0.00285 AC XY: 325 AN XY: 113836

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.000693

Gnomad ASJ exome AF: 0.00356

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00646

Gnomad NFE exome AF: 0.00429

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00354 AC: 5092 AN: 1440056 Hom.: 17 Cov.: 31 AF XY: 0.00351 AC XY: 2507 AN XY: 714250

Gnomad4 AFR exome AF: 0.000302

Gnomad4 AMR exome AF: 0.000727

Gnomad4 ASJ exome AF: 0.00420

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.0000841

Gnomad4 FIN exome AF: 0.00783

Gnomad4 NFE exome AF: 0.00397

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.00307 AC: 468 AN: 152276 Hom.: 4 Cov.: 32 AF XY: 0.00302 AC XY: 225 AN XY: 74454

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00782

Gnomad4 NFE AF: 0.00479

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00362 Hom.: 7

Bravo AF: 0.00212

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.0080
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: rs140322567; hg19: chr16-3118240;