rs34412950

Variant names:

• chr20-45176491-C-A
• rs34412950
• NM_002638.4:c.*123C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45176491-C-A
• chr20-45176491-C-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.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 252,610 control chromosomes in the GnomAD database, including 3,431 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 (1996 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1435 hom.)
• Consequence: PI3 NM_002638.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 7 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4	c.*123C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.*123C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23844 AN: 151990 Hom.: 1988 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.161 AC: 16137 AN: 100502 Hom.: 1435 Cov.: 0 AF XY: 0.159 AC XY: 8308 AN XY: 52092

African (AFR) AF: 0.107 AC: 382 AN: 3560

American (AMR) AF: 0.113 AC: 560 AN: 4940

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 617 AN: 3200

East Asian (EAS) AF: 0.0179 AC: 100 AN: 5600

South Asian (SAS) AF: 0.157 AC: 1622 AN: 10330

European-Finnish (FIN) AF: 0.186 AC: 830 AN: 4452

Middle Eastern (MID) AF: 0.236 AC: 109 AN: 462

European-Non Finnish (NFE) AF: 0.176 AC: 10912 AN: 61912

Other (OTH) AF: 0.166 AC: 1005 AN: 6046

GnomAD4 genome AF: 0.157 AC: 23891 AN: 152108 Hom.: 1996 Cov.: 32 AF XY: 0.157 AC XY: 11691 AN XY: 74354

African (AFR) AF: 0.124 AC: 5162 AN: 41504

American (AMR) AF: 0.134 AC: 2054 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5184

South Asian (SAS) AF: 0.146 AC: 701 AN: 4814

European-Finnish (FIN) AF: 0.192 AC: 2036 AN: 10582

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12369 AN: 67950

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.111 Hom.: 218

Bravo AF: 0.151

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.45
PhyloP100		-0.27
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: rs34412950; hg19: chr20-43805132;