rs6032040

Variant names:

• chr20-45175673-A-T
• rs6032040
• NM_002638.4:c.80-188A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002638.4(PI3):​c.80-188A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,070 control chromosomes in the GnomAD database, including 49,694 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 0.81 (49694 hom., cov: 30)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4	c.80-188A>T		intron_variant	Intron 1 of 2	ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.80-188A>T		intron_variant	Intron 1 of 2	1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122585 AN: 151952 Hom.: 49644 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.811

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.807 AC: 122688 AN: 152070 Hom.: 49694 Cov.: 30 AF XY: 0.805 AC XY: 59834 AN XY: 74338

African (AFR) AF: 0.755 AC: 31299 AN: 41448

American (AMR) AF: 0.756 AC: 11554 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2711 AN: 3468

East Asian (EAS) AF: 0.923 AC: 4764 AN: 5162

South Asian (SAS) AF: 0.867 AC: 4179 AN: 4820

European-Finnish (FIN) AF: 0.814 AC: 8603 AN: 10572

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56823 AN: 67992

Other (OTH) AF: 0.813 AC: 1717 AN: 2112

Alfa AF: 0.814 Hom.: 6265

Bravo AF: 0.803

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.46
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6032040; hg19: chr20-43804314;