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. Variant has been reported in ClinVar as (no stars).

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335025.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPIL2	NM_014337.4	MANE Select	c.*4C>T	3_prime_UTR	Exon 20 of 20	NP_055152.1	Q13356-1
PPIL2	NM_001317996.2		c.*4C>T	splice_region	Exon 20 of 21	NP_001304925.1	Q13356-1
PPIL2	NM_148175.3		c.*4C>T	splice_region	Exon 20 of 21	NP_680480.1	Q13356-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPIL2	ENST00000335025.12	TSL:1	c.*4C>T		splice_region	Exon 20 of 21	ENSP00000334553.7	Q13356-1
PPIL2	ENST00000406385.1	TSL:1	c.*4C>T		splice_region	Exon 20 of 21	ENSP00000384299.1	Q13356-1
PPIL2	ENST00000626352.2	TSL:1	c.1563C>T	p.Ser521Ser	splice_region synonymous	Exon 20 of 21	ENSP00000486725.1	Q13356-2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over