Genetic Variant ENST00000335025.12:c.*4C>T (chr22-21695494-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000335025.12(PPIL2):c.*4C>T variant causes a splice region 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
ENST00000335025.12 splice_region

Scores

Splicing: ADA: 0.9465

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.739

Publications

30 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.014).

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 link	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 link	c.*4C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_014337.4	ENSP00000381812.3		Q13356-1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54941

AN:

152000

Hom.:

10038

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.359

AC:

75783

AN:

211176

AF XY:

0.355

show subpopulations

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 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.:

AF XY:

0.339

AC XY:

241293

AN XY:

712640

show subpopulations

African (AFR)

AF:

0.387

AC:

12812

AN:

33092

American (AMR)

AF:

0.366

AC:

15013

AN:

41008

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10302

AN:

25642

East Asian (EAS)

AF:

0.417

AC:

16209

AN:

38824

South Asian (SAS)

AF:

0.326

AC:

27024

AN:

82810

European-Finnish (FIN)

AF:

0.404

AC:

20825

AN:

51536

Middle Eastern (MID)

AF:

0.321

AC:

1823

AN:

5682

European-Non Finnish (NFE)

AF:

0.330

AC:

362664

AN:

1099378

Other (OTH)

AF:

0.342

AC:

20350

AN:

59512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

21334

42668

64002

85336

106670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11864

23728

35592

47456

59320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.361

AC:

54989

AN:

152120

Hom.:

10052

Cov.:

AF XY:

0.365

AC XY:

27108

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.384

AC:

15930

AN:

41488

American (AMR)

AF:

0.335

AC:

5120

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1459

AN:

3472

East Asian (EAS)

AF:

0.431

AC:

2230

AN:

5174

South Asian (SAS)

AF:

0.315

AC:

1518

AN:

4820

European-Finnish (FIN)

AF:

0.432

AC:

4572

AN:

10586

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23089

AN:

67972

Other (OTH)

AF:

0.351

AC:

741

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1848

3697

5545

7394

9242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.353

Hom.:

10117

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

(source)

DANN

Uncertain

0.99

PhyloP100

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over