rs17333180

chr20-45175067-C-A

Variant summary

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

The NM_002638.4(PI3):c.79+66C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,282,582 control chromosomes in the GnomAD database, including 17,689 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 0.15 (1923 hom., cov: 32)
  • Exomes 𝑓: 0.16 (15766 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI3	NM_002638.4	c.79+66C>A		intron_variant		ENST00000243924.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI3	ENST00000243924.4	c.79+66C>A		intron_variant		1	NM_002638.4	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23279 AN: 152104 Hom.: 1918 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.161 AC: 182054 AN: 1130360 Hom.: 15766 AF XY: 0.162 AC XY: 91718 AN XY: 567072

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0884

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.153 AC: 23317 AN: 152222 Hom.: 1923 Cov.: 32 AF XY: 0.154 AC XY: 11479 AN XY: 74404

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0353

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.165

Alfa AF: 0.172 Hom.: 2324

Bravo AF: 0.147

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.37
Dann	Benign	0.54

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: rs17333180; hg19: chr20-43803708;