rs34885285

Variant names:

• chr20-45176148-C-A
• rs34885285
• NM_002638.4:c.*1+12C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45176148-C-A
• chr20-45176148-C-G

Variant summary

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

The NM_002638.4(PI3):​c.*1+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,611,264 control chromosomes in the GnomAD database, including 26,110 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 (1980 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24130 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI3	NM_002638.4	MANE Select	c.*1+12C>A		intron	N/A	NP_002629.1	P19957

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI3	ENST00000243924.4	TSL:1 MANE Select	c.*1+12C>A		intron	N/A	ENSP00000243924.3	P19957
	PI3	ENST00000971330.1		c.*1+12C>A		intron	N/A	ENSP00000641389.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23770 AN: 151822 Hom.: 1976 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.155 AC: 38748 AN: 250646 AF XY: 0.160

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0305

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.177 AC: 257921 AN: 1459326 Hom.: 24130 Cov.: 32 AF XY: 0.176 AC XY: 128084 AN XY: 725940

African (AFR) AF: 0.120 AC: 4029 AN: 33446

American (AMR) AF: 0.0929 AC: 4154 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5050 AN: 26106

East Asian (EAS) AF: 0.0199 AC: 791 AN: 39694

South Asian (SAS) AF: 0.167 AC: 14377 AN: 86208

European-Finnish (FIN) AF: 0.194 AC: 10370 AN: 53364

Middle Eastern (MID) AF: 0.201 AC: 1139 AN: 5656

European-Non Finnish (NFE) AF: 0.187 AC: 207890 AN: 1109834

Other (OTH) AF: 0.168 AC: 10121 AN: 60308

GnomAD4 genome AF: 0.157 AC: 23807 AN: 151938 Hom.: 1980 Cov.: 31 AF XY: 0.157 AC XY: 11646 AN XY: 74270

African (AFR) AF: 0.124 AC: 5143 AN: 41464

American (AMR) AF: 0.134 AC: 2050 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3466

East Asian (EAS) AF: 0.0325 AC: 168 AN: 5176

South Asian (SAS) AF: 0.144 AC: 691 AN: 4808

European-Finnish (FIN) AF: 0.191 AC: 2014 AN: 10538

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12348 AN: 67926

Other (OTH) AF: 0.165 AC: 346 AN: 2100

Alfa AF: 0.176 Hom.: 454

Bravo AF: 0.151

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.57
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34885285; hg19: chr20-43804789; COSMIC: COSV54783872;