rs1983649

chr20-45175084-T-Achr20-45175084-T-Cchr20-45175084-T-G

Variant summary

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

The NM_002638.4(PI3):c.79+83T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 969,942 control chromosomes in the GnomAD database, including 162,182 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 0.52 (21296 hom., cov: 32)
  • Exomes 𝑓: 0.58 (140886 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI3	NM_002638.4	c.79+83T>A		intron_variant		ENST00000243924.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI3	ENST00000243924.4	c.79+83T>A		intron_variant		1	NM_002638.4	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79564 AN: 152002 Hom.: 21297 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.584 AC: 478013 AN: 817822 Hom.: 140886 AF XY: 0.586 AC XY: 244521 AN XY: 417568

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.523 AC: 79583 AN: 152120 Hom.: 21296 Cov.: 32 AF XY: 0.517 AC XY: 38464 AN XY: 74346

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.527

Alfa AF: 0.413 Hom.: 1091

Bravo AF: 0.516

Asia WGS AF: 0.564 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.8
Dann	Benign	0.63

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: rs1983649; hg19: chr20-43803725; COSMIC: COSV54783026;