chr16-3067353-T-G

Variant names:

• chr16-3067353-T-G
• rs1555001
• NM_001376923.1:c.16-24T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376923.1(IL32):​c.16-24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000801 in 1,248,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: IL32 NM_001376923.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 17 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376923.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	NM_001376923.1	MANE Select	c.16-24T>G		intron	N/A	NP_001363852.1
	IL32	NM_001308078.4		c.16-24T>G		intron	N/A	NP_001295007.1
	IL32	NM_001369587.3		c.16-24T>G		intron	N/A	NP_001356516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	ENST00000525643.7	TSL:1 MANE Select	c.16-24T>G		intron	N/A	ENSP00000432218.3
	IL32	ENST00000396890.6	TSL:1	c.16-24T>G		intron	N/A	ENSP00000380099.2
	IL32	ENST00000325568.9	TSL:1	c.16-24T>G		intron	N/A	ENSP00000324742.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000539 AC: 1 AN: 185498 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000801 AC: 10 AN: 1248626 Hom.: 0 Cov.: 18 AF XY: 0.0000113 AC XY: 7 AN XY: 619006

African (AFR) AF: 0.00 AC: 0 AN: 27696

American (AMR) AF: 0.00 AC: 0 AN: 31424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19700

East Asian (EAS) AF: 0.00 AC: 0 AN: 38360

South Asian (SAS) AF: 0.000115 AC: 8 AN: 69468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5058

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 954564

Other (OTH) AF: 0.0000382 AC: 2 AN: 52306

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.60
PhyloP100		0.12
BranchPoint Hunter		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1555001; hg19: chr16-3117354;