Genetic Variant NM_002638.4:c.79+83T>A (chr20-45175084-T-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+83T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 969,942 control chromosomes in the GnomAD database, including 162,182 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 0.52 ( 21296 hom., cov: 32)

Exomes 𝑓: 0.58 ( 140886 hom. )

Consequence

PI3
NM_002638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.595

Publications

6 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4 link	c.79+83T>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+83T>A		intron_variant	Intron 1 of 2	1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79564

AN:

152002

Hom.:

21297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.515

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.529

GnomAD4 exome

AF:

0.584

AC:

478013

AN:

817822

Hom.:

140886

AF XY:

0.586

AC XY:

244521

AN XY:

417568

show subpopulations

African (AFR)

AF:

0.416

AC:

7824

AN:

18828

American (AMR)

AF:

0.510

AC:

13128

AN:

25730

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

8191

AN:

15904

East Asian (EAS)

AF:

0.495

AC:

15982

AN:

32288

South Asian (SAS)

AF:

0.578

AC:

32630

AN:

56450

European-Finnish (FIN)

AF:

0.541

AC:

25448

AN:

47068

Middle Eastern (MID)

AF:

0.560

AC:

1824

AN:

3256

European-Non Finnish (NFE)

AF:

0.605

AC:

351564

AN:

581142

Other (OTH)

AF:

0.577

AC:

21422

AN:

37156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

9620

19241

28861

38482

48102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7838

15676

23514

31352

39190

<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:

0.523

AC:

79583

AN:

152120

Hom.:

21296

Cov.:

AF XY:

0.517

AC XY:

38464

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.410

AC:

16991

AN:

41484

American (AMR)

AF:

0.484

AC:

7403

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

1786

AN:

3466

East Asian (EAS)

AF:

0.559

AC:

2889

AN:

5172

South Asian (SAS)

AF:

0.587

AC:

2830

AN:

4818

European-Finnish (FIN)

AF:

0.532

AC:

5631

AN:

10584

Middle Eastern (MID)

AF:

0.551

AC:

161

AN:

292

European-Non Finnish (NFE)

AF:

0.593

AC:

40315

AN:

67988

Other (OTH)

AF:

0.527

AC:

1115

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1955

3910

5866

7821

9776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.413

Hom.:

1091

Bravo

AF:

0.516

Asia WGS

AF:

0.564

AC:

1961

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.63

PhyloP100

0.59

PromoterAI

-0.041

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