rs17333381

chr20-45176278-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002638.4(PI3):c.*2-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 731,790 control chromosomes in the GnomAD database, including 10,085 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.

• Frequency:
  • Genomes: 𝑓 0.16 (2024 hom., cov: 31)
  • Exomes 𝑓: 0.16 (8061 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

Genes affected

PI3 (HGNC:8947): (peptidase inhibitor 3) This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. Expression of this gene is upgulated by bacterial lipopolysaccharides and cytokines. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI3	NM_002638.4	c.*2-92C>T		intron_variant		ENST00000243924.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI3	ENST00000243924.4	c.*2-92C>T		intron_variant		1	NM_002638.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23884 AN: 151912 Hom.: 2019 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.159 AC: 92329 AN: 579760 Hom.: 8061 Cov.: 7 AF XY: 0.160 AC XY: 48697 AN XY: 304108

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0184

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.157 AC: 23923 AN: 152030 Hom.: 2024 Cov.: 31 AF XY: 0.158 AC XY: 11725 AN XY: 74338

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.168

Alfa AF: 0.171 Hom.: 280

Bravo AF: 0.151

Asia WGS AF: 0.0930 AC: 322 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs17333381; hg19: chr20-43804919;