16-3067373-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001376923.1(IL32):c.16-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,525,326 control chromosomes in the GnomAD database, including 3 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 0.0011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (2 hom.)
• Consequence: IL32 NM_001376923.1 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001981
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-3067373-G-A is Benign according to our data. Variant chr16-3067373-G-A is described in ClinVar as [Benign]. Clinvar id is 727408.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL32	NM_001376923.1	c.16-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000525643.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL32	ENST00000525643.7	c.16-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001376923.1	A2

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 166 AN: 151416 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000487 AC: 93 AN: 191042 Hom.: 1 AF XY: 0.000375 AC XY: 38 AN XY: 101286

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.000641

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000288

Gnomad FIN exome AF: 0.0000563

Gnomad NFE exome AF: 0.0000764

Gnomad OTH exome AF: 0.000458

GnomAD4 exome AF: 0.000168 AC: 231 AN: 1373796 Hom.: 2 Cov.: 31 AF XY: 0.000157 AC XY: 106 AN XY: 676422

Gnomad4 AFR exome AF: 0.00396

Gnomad4 AMR exome AF: 0.000494

Gnomad4 ASJ exome AF: 0.0000479

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.0000451

Gnomad4 OTH exome AF: 0.000442

GnomAD4 genome AF: 0.00112 AC: 169 AN: 151530 Hom.: 1 Cov.: 31 AF XY: 0.00113 AC XY: 84 AN XY: 74024

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.000856 Hom.: 0

Bravo AF: 0.00122

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs190241571; hg19: chr16-3117374;