rs45461302

Variant names:

• chr20-45176633-G-A
• rs45461302
• NM_002638.4:c.*265G>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• 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=-0.91).
• 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.*265G>A		downstream_gene	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.*265G>A		downstream_gene	N/A	ENSP00000243924.3	P19957
	PI3	ENST00000971330.1		c.*263G>A		downstream_gene	N/A	ENSP00000641389.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23816 AN: 151948 Hom.: 1981 Cov.: 32

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.: 87 AF XY: 0.133 AC XY: 557 AN XY: 4194

African (AFR) AF: 0.0698 AC: 6 AN: 86

American (AMR) AF: 0.0921 AC: 136 AN: 1476

Ashkenazi Jewish (ASJ) AF: 0.0909 AC: 6 AN: 66

East Asian (EAS) AF: 0.0232 AC: 7 AN: 302

South Asian (SAS) AF: 0.135 AC: 128 AN: 948

European-Finnish (FIN) AF: 0.154 AC: 20 AN: 130

Middle Eastern (MID) AF: 0.350 AC: 7 AN: 20

European-Non Finnish (NFE) AF: 0.151 AC: 682 AN: 4512

Other (OTH) AF: 0.125 AC: 38 AN: 304

GnomAD4 genome AF: 0.157 AC: 23855 AN: 152066 Hom.: 1986 Cov.: 32 AF XY: 0.157 AC XY: 11677 AN XY: 74312

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: 71 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12358 AN: 67950

Other (OTH) AF: 0.166 AC: 350 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.70
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs45461302; hg19: chr20-43805274;