rs34412950

Positions:

• chr20-45176491-C-A
• chr20-45176491-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.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 252,610 control chromosomes in the GnomAD database, including 3,431 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 (1996 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1435 hom.)
• Consequence: PI3 NM_002638.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.91).
• 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.*123C>A		3_prime_UTR_variant	3/3	ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.*123C>A		3_prime_UTR_variant	3/3	1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23844 AN: 151990 Hom.: 1988 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.161 AC: 16137 AN: 100502 Hom.: 1435 Cov.: 0 AF XY: 0.159 AC XY: 8308 AN XY: 52092

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.0179

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.157 AC: 23891 AN: 152108 Hom.: 1996 Cov.: 32 AF XY: 0.157 AC XY: 11691 AN XY: 74354

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.168

Alfa AF: 0.110 Hom.: 213

Bravo AF: 0.151

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
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: rs34412950; hg19: chr20-43805132;