chr20-45176148-C-A

Position:

• chr20-45176148-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.*1+12C>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 1,611,264 control chromosomes in the GnomAD database, including 26,110 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 (1980 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24130 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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=-0.87).
• 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	Protein	UniProt
PI3	NM_002638.4	c.*1+12C>A		intron_variant		ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.*1+12C>A		intron_variant		1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23770 AN: 151822 Hom.: 1976 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.155 AC: 38748 AN: 250646 Hom.: 3435 AF XY: 0.160 AC XY: 21686 AN XY: 135470

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0884

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: 257921 AN: 1459326 Hom.: 24130 Cov.: 32 AF XY: 0.176 AC XY: 128084 AN XY: 725940

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0929

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: 23807 AN: 151938 Hom.: 1980 Cov.: 31 AF XY: 0.157 AC XY: 11646 AN XY: 74270

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 449

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	-0.87
CADD	Benign	0.88
DANN	Benign	0.57

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: rs34885285; hg19: chr20-43804789; COSMIC: COSV54783872;