22-21695494-C-T

Variant names:

• chr22-21695494-C-T
• rs12484060
• ENST00000335025.12:c.*4C>T

Variant summary

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

The NM_148176.3(PPIL2):​c.1563C>T​(p.Ser521Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,589,604 control chromosomes in the GnomAD database, including 93,397 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10052 hom., cov: 33)
  • Exomes 𝑓: 0.34 (83345 hom.)
• Consequence: PPIL2 NM_148176.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.9465
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL2	NM_014337.4	c.*4C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000398831.8	NP_055152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL2	ENST00000398831.8	c.*4C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_014337.4	ENSP00000381812.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54941 AN: 152000 Hom.: 10038 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.359 AC: 75783 AN: 211176 Hom.: 13672 AF XY: 0.355 AC XY: 40369 AN XY: 113722

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.430

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.339 AC: 487022 AN: 1437484 Hom.: 83345 Cov.: 37 AF XY: 0.339 AC XY: 241293 AN XY: 712640

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.361 AC: 54989 AN: 152120 Hom.: 10052 Cov.: 33 AF XY: 0.365 AC XY: 27108 AN XY: 74366

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.351

Alfa AF: 0.348 Hom.: 5913

Bravo AF: 0.358

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Uncertain	24
DANN	Uncertain	0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Benign	0.70
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.86		Position offset: -2
DS_DL_spliceai		0.34		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12484060; hg19: chr22-22049783; COSMIC: COSV58605121; COSMIC: COSV58605121;