rs5999098

Positions:

• chr22-21694573-C-T

Variant summary

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

The NM_014337.4(PPIL2):​c.1197-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,288 control chromosomes in the GnomAD database, including 96,778 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 0.37 (10506 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86272 hom.)
• Consequence: PPIL2 NM_014337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.78).
• 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/exons	MANE	UniProt
PPIL2	NM_014337.4	c.1197-20C>T		intron_variant		ENST00000398831.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIL2	ENST00000398831.8	c.1197-20C>T		intron_variant		1	NM_014337.4	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56116 AN: 151856 Hom.: 10491 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.356

GnomAD3 exomes AF: 0.365 AC: 91589 AN: 250912 Hom.: 17060 AF XY: 0.360 AC XY: 48850 AN XY: 135626

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.432

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.342 AC: 499075 AN: 1461314 Hom.: 86272 Cov.: 38 AF XY: 0.341 AC XY: 248018 AN XY: 726996

Gnomad4 AFR exome AF: 0.418

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.370 AC: 56164 AN: 151974 Hom.: 10506 Cov.: 32 AF XY: 0.372 AC XY: 27651 AN XY: 74276

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.355

Alfa AF: 0.344 Hom.: 15851

Bravo AF: 0.368

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5999098; hg19: chr22-22048862; COSMIC: COSV58608912; COSMIC: COSV58608912;