Genetic Variant NM_002638.4:c.*125G>C (chr20-45176493-G-C) – 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.*125G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 250,550 control chromosomes in the GnomAD database, including 3,429 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 ( 1996 hom., cov: 32)

Exomes 𝑓: 0.16 ( 1433 hom. )

Consequence

PI3
NM_002638.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

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=-0.91).

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.*125G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000243924.4	NP_002629.1	P19957

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4 link	c.*125G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23848

AN:

151900

Hom.:

1988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0326

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.161

AC:

15890

AN:

98532

Hom.:

1433

Cov.:

AF XY:

0.160

AC XY:

8174

AN XY:

51022

show subpopulations

African (AFR)

AF:

0.110

AC:

383

AN:

3486

American (AMR)

AF:

0.114

AC:

559

AN:

4898

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

609

AN:

3110

East Asian (EAS)

AF:

0.0182

AC:

AN:

5398

South Asian (SAS)

AF:

0.156

AC:

1611

AN:

10320

European-Finnish (FIN)

AF:

0.183

AC:

789

AN:

4318

Middle Eastern (MID)

AF:

0.239

AC:

107

AN:

448

European-Non Finnish (NFE)

AF:

0.177

AC:

10748

AN:

60666

Other (OTH)

AF:

0.167

AC:

986

AN:

5888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

650

1300

1949

2599

3249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

23895

AN:

152018

Hom.:

1996

Cov.:

AF XY:

0.157

AC XY:

11693

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.124

AC:

5163

AN:

41474

American (AMR)

AF:

0.134

AC:

2053

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3472

East Asian (EAS)

AF:

0.0324

AC:

168

AN:

5180

South Asian (SAS)

AF:

0.146

AC:

701

AN:

4806

European-Finnish (FIN)

AF:

0.193

AC:

2037

AN:

10564

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12370

AN:

67938

Other (OTH)

AF:

0.168

AC:

355

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1013

2025

3038

4050

5063

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:

0.171

Hom.:

278

Bravo

AF:

0.151

Asia WGS

AF:

0.0940

AC:

325

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.63

(source)

DANN

Benign

0.58

PhyloP100

-1.8

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