rs4035022

Variant names:

• chr2-200879629-G-A
• rs4035022
• NM_130906.3:c.240+1792C>T

Variant summary

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

The NM_130906.3(PPIL3):​c.240+1792C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,144 control chromosomes in the GnomAD database, including 1,871 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 0.15 (1871 hom., cov: 32)
• Consequence: PPIL3 NM_130906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 7 publications found

Genes affected

PPIL3 (HGNC:9262): (peptidylprolyl isomerase like 3) This gene encodes a member of the cyclophilin family. Cyclophilins catalyze the cis-trans isomerization of peptidylprolyl imide bonds in oligopeptides. They have been proposed to act either as catalysts or as molecular chaperones in protein-folding events. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL3	NM_130906.3	c.240+1792C>T		intron_variant	Intron 5 of 6	ENST00000392283.9	NP_570981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL3	ENST00000392283.9	c.240+1792C>T		intron_variant	Intron 5 of 6	1	NM_130906.3	ENSP00000376107.4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22424 AN: 152026 Hom.: 1869 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22440 AN: 152144 Hom.: 1871 Cov.: 32 AF XY: 0.143 AC XY: 10624 AN XY: 74388

African (AFR) AF: 0.199 AC: 8253 AN: 41498

American (AMR) AF: 0.127 AC: 1940 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3470

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5174

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4826

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9874 AN: 67992

Other (OTH) AF: 0.146 AC: 308 AN: 2110

Alfa AF: 0.153 Hom.: 244

Bravo AF: 0.154

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		0.34
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: rs4035022; hg19: chr2-201744352;