20-45176156-C-A

Variant names:

• chr20-45176156-C-A
• rs17424474
• NM_002638.4:c.*1+20C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PI3	NM_002638.4	c.*1+20C>A		intron_variant	Intron 2 of 2	ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.*1+20C>A		intron_variant	Intron 2 of 2	1	NM_002638.4	ENSP00000243924.3

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

GnomAD2 exomes AF: 0.154 AC: 38613 AN: 250172 AF XY: 0.160

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 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

African (AFR) AF: 0.120 AC: 4019 AN: 33414

American (AMR) AF: 0.0928 AC: 4149 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5043 AN: 26080

East Asian (EAS) AF: 0.0199 AC: 791 AN: 39682

South Asian (SAS) AF: 0.167 AC: 14370 AN: 86182

European-Finnish (FIN) AF: 0.194 AC: 10355 AN: 53336

Middle Eastern (MID) AF: 0.202 AC: 1120 AN: 5540

European-Non Finnish (NFE) AF: 0.187 AC: 207467 AN: 1108786

Other (OTH) AF: 0.168 AC: 10102 AN: 60254

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

African (AFR) AF: 0.124 AC: 5149 AN: 41468

American (AMR) AF: 0.134 AC: 2048 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3468

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5170

South Asian (SAS) AF: 0.144 AC: 692 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2012 AN: 10506

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12361 AN: 67922

Other (OTH) AF: 0.166 AC: 349 AN: 2108

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
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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