dbSNP rs45461302: PI3:c.*265G>A (chr20-45176633-G-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.*265G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 159,910 control chromosomes in the GnomAD database, including 2,073 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 ( 1986 hom., cov: 32)

Exomes 𝑓: 0.13 ( 87 hom. )

Consequence

PI3
NM_002638.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.733

Publications

3 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.*265G>A		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.*265G>A		downstream_gene_variant		1	NM_002638.4	ENSP00000243924.3		P19957

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23816

AN:

151948

Hom.:

1981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.131

AC:

1030

AN:

7844

Hom.:

AF XY:

0.133

AC XY:

557

AN XY:

4194

show subpopulations

African (AFR)

AF:

0.0698

AC:

AN:

American (AMR)

AF:

0.0921

AC:

136

AN:

1476

Ashkenazi Jewish (ASJ)

AF:

0.0909

AC:

AN:

East Asian (EAS)

AF:

0.0232

AC:

AN:

302

South Asian (SAS)

AF:

0.135

AC:

128

AN:

948

European-Finnish (FIN)

AF:

0.154

AC:

AN:

130

Middle Eastern (MID)

AF:

0.350

AC:

AN:

European-Non Finnish (NFE)

AF:

0.151

AC:

682

AN:

4512

Other (OTH)

AF:

0.125

AC:

AN:

304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

122

163

204

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:

0.157

AC:

23855

AN:

152066

Hom.:

1986

Cov.:

AF XY:

0.157

AC XY:

11677

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.124

AC:

5143

AN:

41502

American (AMR)

AF:

0.134

AC:

2054

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3472

East Asian (EAS)

AF:

0.0326

AC:

169

AN:

5178

South Asian (SAS)

AF:

0.145

AC:

699

AN:

4820

European-Finnish (FIN)

AF:

0.192

AC:

2032

AN:

10560

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12358

AN:

67950

Other (OTH)

AF:

0.166

AC:

350

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1025

2050

3074

4099

5124

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.:

3032

Bravo

AF:

0.151

Asia WGS

AF:

0.0920

AC:

320

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

0.30

(source)

DANN

Benign

0.70

PhyloP100

-0.73

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