Genetic Variant PI3:c.*1+12C>A (chr20-45176148-C-A) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.962

Publications

11 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=-0.87).

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 rank	MANE	Protein	UniProt
PI3	NM_002638.4 link	c.*1+12C>A		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.*1+12C>A		intron_variant	Intron 2 of 2	1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23770

AN:

151822

Hom.:

1976

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.155

AC:

38748

AN:

250646

AF XY:

0.160

show subpopulations

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 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.:

AF XY:

0.176

AC XY:

128084

AN XY:

725940

show subpopulations

African (AFR)

AF:

0.120

AC:

4029

AN:

33446

American (AMR)

AF:

0.0929

AC:

4154

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

5050

AN:

26106

East Asian (EAS)

AF:

0.0199

AC:

791

AN:

39694

South Asian (SAS)

AF:

0.167

AC:

14377

AN:

86208

European-Finnish (FIN)

AF:

0.194

AC:

10370

AN:

53364

Middle Eastern (MID)

AF:

0.201

AC:

1139

AN:

5656

European-Non Finnish (NFE)

AF:

0.187

AC:

207890

AN:

1109834

Other (OTH)

AF:

0.168

AC:

10121

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

9103

18206

27308

36411

45514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7198

14396

21594

28792

35990

<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:

23807

AN:

151938

Hom.:

1980

Cov.:

AF XY:

0.157

AC XY:

11646

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.124

AC:

5143

AN:

41464

American (AMR)

AF:

0.134

AC:

2050

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3466

East Asian (EAS)

AF:

0.0325

AC:

168

AN:

5176

South Asian (SAS)

AF:

0.144

AC:

691

AN:

4808

European-Finnish (FIN)

AF:

0.191

AC:

2014

AN:

10538

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.182

AC:

12348

AN:

67926

Other (OTH)

AF:

0.165

AC:

346

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

989

1979

2968

3958

4947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.176

Hom.:

454

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

(source)

DANN

Benign

0.57

PhyloP100

-0.96

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