dbSNP rs17333180: PI3:c.79+66C>A (chr20-45175067-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.79+66C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,282,582 control chromosomes in the GnomAD database, including 17,689 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 0.15 ( 1923 hom., cov: 32)

Exomes 𝑓: 0.16 ( 15766 hom. )

Consequence

PI3
NM_002638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

10 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:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4 link	c.79+66C>A		intron_variant	Intron 1 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.79+66C>A		intron_variant	Intron 1 of 2	1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23279

AN:

152104

Hom.:

1918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.161

AC:

182054

AN:

1130360

Hom.:

15766

AF XY:

0.162

AC XY:

91718

AN XY:

567072

show subpopulations

African (AFR)

AF:

0.114

AC:

2966

AN:

26084

American (AMR)

AF:

0.0884

AC:

3192

AN:

36096

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4048

AN:

20250

East Asian (EAS)

AF:

0.0207

AC:

735

AN:

35562

South Asian (SAS)

AF:

0.161

AC:

11467

AN:

71362

European-Finnish (FIN)

AF:

0.188

AC:

9481

AN:

50328

Middle Eastern (MID)

AF:

0.192

AC:

842

AN:

4384

European-Non Finnish (NFE)

AF:

0.169

AC:

141718

AN:

838040

Other (OTH)

AF:

0.158

AC:

7605

AN:

48254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6864

13727

20591

27454

34318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4602

9204

13806

18408

23010

<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:

0.153

AC:

23317

AN:

152222

Hom.:

1923

Cov.:

AF XY:

0.154

AC XY:

11479

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.123

AC:

5101

AN:

41524

American (AMR)

AF:

0.130

AC:

1988

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

731

AN:

3466

East Asian (EAS)

AF:

0.0353

AC:

183

AN:

5178

South Asian (SAS)

AF:

0.146

AC:

704

AN:

4818

European-Finnish (FIN)

AF:

0.191

AC:

2027

AN:

10608

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11879

AN:

68012

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1043

2086

3128

4171

5214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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.:

2939

Bravo

AF:

0.147

Asia WGS

AF:

0.0930

AC:

323

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.37

(source)

DANN

Benign

0.54

PhyloP100

-1.1

PromoterAI

0.013

Neutral

(source)

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