20-45175084-T-C

Variant names:

• chr20-45175084-T-C
• rs1983649
• NM_002638.4:c.79+83T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002638.4(PI3):​c.79+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 971,964 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 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: PI3 NM_002638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 6 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4	c.79+83T>C		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.79+83T>C		intron_variant	Intron 1 of 2	1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000500 AC: 41 AN: 819900 Hom.: 0 AF XY: 0.0000358 AC XY: 15 AN XY: 418600

African (AFR) AF: 0.00 AC: 0 AN: 18882

American (AMR) AF: 0.00 AC: 0 AN: 25824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15936

East Asian (EAS) AF: 0.00 AC: 0 AN: 32326

South Asian (SAS) AF: 0.00 AC: 0 AN: 56596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3268

European-Non Finnish (NFE) AF: 0.0000704 AC: 41 AN: 582680

Other (OTH) AF: 0.00 AC: 0 AN: 37240

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74254

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 1091

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.66
PhyloP100		0.59
PromoterAI		-0.013	Neutral

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: rs1983649; hg19: chr20-43803725;