Genetic Variant PI3:c.*2-92C>T (chr20-45176278-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002638.4(PI3):c.*2-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 731,790 control chromosomes in the GnomAD database, including 10,085 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 ( 2024 hom., cov: 31)

Exomes 𝑓: 0.16 ( 8061 hom. )

Consequence

PI3
NM_002638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.682

Publications

2 publications found

Variant links:

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]

PI3 links:

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ACMG classification

Classification was made for transcript

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 = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4 link	c.*2-92C>T		intron_variant	Intron 2 of 2	ENST00000243924.4	NP_002629.1	P19957

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4 link	c.*2-92C>T		intron_variant	Intron 2 of 2	1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23884

AN:

151912

Hom.:

2019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0326

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.159

AC:

92329

AN:

579760

Hom.:

8061

Cov.:

AF XY:

0.160

AC XY:

48697

AN XY:

304108

show subpopulations

African (AFR)

AF:

0.118

AC:

1798

AN:

15174

American (AMR)

AF:

0.104

AC:

2303

AN:

22194

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

2858

AN:

15050

East Asian (EAS)

AF:

0.0184

AC:

601

AN:

32598

South Asian (SAS)

AF:

0.164

AC:

8311

AN:

50732

European-Finnish (FIN)

AF:

0.191

AC:

6297

AN:

33004

Middle Eastern (MID)

AF:

0.202

AC:

452

AN:

2240

European-Non Finnish (NFE)

AF:

0.171

AC:

64708

AN:

378104

Other (OTH)

AF:

0.163

AC:

5001

AN:

30664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

3927

7854

11780

15707

19634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.157

AC:

23923

AN:

152030

Hom.:

2024

Cov.:

AF XY:

0.158

AC XY:

11725

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.124

AC:

5160

AN:

41470

American (AMR)

AF:

0.135

AC:

2058

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3470

East Asian (EAS)

AF:

0.0325

AC:

168

AN:

5168

South Asian (SAS)

AF:

0.144

AC:

694

AN:

4808

European-Finnish (FIN)

AF:

0.193

AC:

2044

AN:

10564

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12394

AN:

67954

Other (OTH)

AF:

0.168

AC:

355

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

984

1968

2953

3937

4921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.169

Hom.:

285

Bravo

AF:

0.151

Asia WGS

AF:

0.0930

AC:

322

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

(source)

DANN

Benign

0.45

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over