NM_002638.4:c.*270C>T

Variant names:

• chr20-45176638-C-T
• rs2267864
• NM_002638.4:c.*270C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002638.4(PI3):​c.*270C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 158,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: PI3 NM_002638.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000290 AC: 2 AN: 6894 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3698

African (AFR) AF: 0.00 AC: 0 AN: 66

American (AMR) AF: 0.00 AC: 0 AN: 1286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 66

East Asian (EAS) AF: 0.00 AC: 0 AN: 234

South Asian (SAS) AF: 0.00 AC: 0 AN: 806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.000496 AC: 2 AN: 4036

Other (OTH) AF: 0.00 AC: 0 AN: 274

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151828 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74132

African (AFR) AF: 0.0000484 AC: 2 AN: 41326

American (AMR) AF: 0.000131 AC: 2 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.87
PhyloP100		0.58

Splicing

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

Other links and lift over

dbSNP: rs2267864; hg19: chr20-43805279;