rs12170039

Positions:

• chr22-21692498-G-A
• chr22-21692498-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014337.4(PPIL2):​c.1140-1318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,736 control chromosomes in the GnomAD database, including 13,742 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 0.41 (13742 hom., cov: 30)
• Consequence: PPIL2 NM_014337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

PPIL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL2	NM_014337.4	c.1140-1318G>A		intron_variant		ENST00000398831.8	NP_055152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL2	ENST00000398831.8	c.1140-1318G>A		intron_variant		1	NM_014337.4	ENSP00000381812.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61824 AN: 151620 Hom.: 13708 Cov.: 30

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.408 AC: 61909 AN: 151736 Hom.: 13742 Cov.: 30 AF XY: 0.399 AC XY: 29582 AN XY: 74158

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.376

Alfa AF: 0.374 Hom.: 13957

Bravo AF: 0.425

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12170039; hg19: chr22-22046787;