Genetic Variant NM_002638.4:c.*270C>G (chr20-45176638-C-G) – 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.*270C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 158,766 control chromosomes in the GnomAD database, including 3,232 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 0.20 ( 3115 hom., cov: 32)

Exomes 𝑓: 0.16 ( 117 hom. )

Consequence

PI3
NM_002638.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.577

Publications

4 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4 link	c.*270C>G		downstream_gene_variant		ENST00000243924.4	NP_002629.1	P19957

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4 link	c.*270C>G		downstream_gene_variant		1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30476

AN:

151766

Hom.:

3102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.163

AC:

1122

AN:

6882

Hom.:

117

AF XY:

0.168

AC XY:

621

AN XY:

3692

show subpopulations

African (AFR)

AF:

0.182

AC:

AN:

American (AMR)

AF:

0.160

AC:

206

AN:

1284

Ashkenazi Jewish (ASJ)

AF:

0.0909

AC:

AN:

East Asian (EAS)

AF:

0.103

AC:

AN:

234

South Asian (SAS)

AF:

0.160

AC:

129

AN:

804

European-Finnish (FIN)

AF:

0.200

AC:

AN:

110

Middle Eastern (MID)

AF:

0.438

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

672

AN:

4030

Other (OTH)

AF:

0.162

AC:

AN:

272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.201

AC:

30540

AN:

151884

Hom.:

3115

Cov.:

AF XY:

0.204

AC XY:

15110

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.220

AC:

9112

AN:

41424

American (AMR)

AF:

0.200

AC:

3057

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

522

AN:

5164

South Asian (SAS)

AF:

0.156

AC:

750

AN:

4822

European-Finnish (FIN)

AF:

0.235

AC:

2477

AN:

10530

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13116

AN:

67914

Other (OTH)

AF:

0.207

AC:

435

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1245

2490

3734

4979

6224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.0981

Hom.:

137

Bravo

AF:

0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.5

(source)

DANN

Benign

0.43

PhyloP100

0.58

Splicing

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