rs17424474

chr20-45176156-C-Achr20-45176156-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.*1+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,609,872 control chromosomes in the GnomAD database, including 26,057 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 (1984 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24073 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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 = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI3	NM_002638.4	c.*1+20C>A		intron_variant		ENST00000243924.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI3	ENST00000243924.4	c.*1+20C>A		intron_variant		1	NM_002638.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23792 AN: 151788 Hom.: 1980 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.154 AC: 38613 AN: 250172 Hom.: 3397 AF XY: 0.160 AC XY: 21600 AN XY: 135200

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0883

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0305

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.177 AC: 257416 AN: 1457968 Hom.: 24073 Cov.: 31 AF XY: 0.176 AC XY: 127838 AN XY: 725278

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0928

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.0199

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.157 AC: 23829 AN: 151904 Hom.: 1984 Cov.: 31 AF XY: 0.157 AC XY: 11649 AN XY: 74222

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0327

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.166

Alfa AF: 0.130 Hom.: 306

Bravo AF: 0.151

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.46

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: rs17424474; hg19: chr20-43804797; COSMIC: COSV54783879;