rs1555001

Positions:

• chr16-3067353-T-A
• chr16-3067353-T-C
• chr16-3067353-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001376923.1(IL32):​c.16-24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,397,976 control chromosomes in the GnomAD database, including 81,628 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.31 (7669 hom., cov: 29)
  • Exomes 𝑓: 0.33 (73959 hom.)
• Consequence: IL32 NM_001376923.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL32	NM_001376923.1	c.16-24T>A		intron_variant		ENST00000525643.7	NP_001363852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL32	ENST00000525643.7	c.16-24T>A		intron_variant		1	NM_001376923.1	ENSP00000432218.3

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46066 AN: 150512 Hom.: 7670 Cov.: 29

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.361 AC: 66992 AN: 185498 Hom.: 13236 AF XY: 0.365 AC XY: 35628 AN XY: 97626

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.600

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.334 AC: 416028 AN: 1247342 Hom.: 73959 Cov.: 18 AF XY: 0.340 AC XY: 210359 AN XY: 618406

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.306 AC: 46081 AN: 150634 Hom.: 7669 Cov.: 29 AF XY: 0.314 AC XY: 23076 AN XY: 73378

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.287

Alfa AF: 0.229 Hom.: 689

Bravo AF: 0.294

Asia WGS AF: 0.476 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.71
BranchPoint Hunter		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555001; hg19: chr16-3117354; COSMIC: COSV50403951; COSMIC: COSV50403951;