Genetic Variant PPIA:c.-56C>G (chr7-44796669-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021130.5(PPIA):c.-56C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 1,500,482 control chromosomes in the GnomAD database, including 3,826 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 0.051 ( 260 hom., cov: 34)

Exomes 𝑓: 0.071 ( 3566 hom. )

Consequence

PPIA
NM_021130.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

16 publications found

Variant links:

Genes affected

PPIA (HGNC:9253): (peptidylprolyl isomerase A) This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [provided by RefSeq, Jul 2008]

PPIA links:

ENSG00000297670 (HGNC:):

ENSG00000297670 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 (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PPIA	NM_021130.5 link	c.-56C>G	upstream_gene_variant	ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2 link	c.-393C>G	upstream_gene_variant		NP_001287910.1
LOC105375259	XR_007060300.1 link	n.-139G>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6 link	c.-56C>G		upstream_gene_variant		1	NM_021130.5	ENSP00000419425.1

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7734

AN:

152220

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0763

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.0280

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0711

Gnomad OTH

AF:

0.0544

GnomAD4 exome

AF:

0.0715

AC:

96339

AN:

1348148

Hom.:

3566

Cov.:

AF XY:

0.0712

AC XY:

48089

AN XY:

675480

show subpopulations

African (AFR)

AF:

0.0116

AC:

366

AN:

31520

American (AMR)

AF:

0.0682

AC:

3015

AN:

44200

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1472

AN:

24962

East Asian (EAS)

AF:

0.0230

AC:

896

AN:

39008

South Asian (SAS)

AF:

0.0654

AC:

5547

AN:

84796

European-Finnish (FIN)

AF:

0.0317

AC:

1660

AN:

52306

Middle Eastern (MID)

AF:

0.0815

AC:

328

AN:

4026

European-Non Finnish (NFE)

AF:

0.0784

AC:

79204

AN:

1010620

Other (OTH)

AF:

0.0679

AC:

3851

AN:

56710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4590

9180

13771

18361

22951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2928

5856

8784

11712

14640

<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:

0.0508

AC:

7731

AN:

152334

Hom.:

260

Cov.:

AF XY:

0.0504

AC XY:

3753

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0140

AC:

582

AN:

41580

American (AMR)

AF:

0.0763

AC:

1168

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3472

East Asian (EAS)

AF:

0.0289

AC:

150

AN:

5184

South Asian (SAS)

AF:

0.0565

AC:

273

AN:

4830

European-Finnish (FIN)

AF:

0.0280

AC:

297

AN:

10608

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0710

AC:

4833

AN:

68034

Other (OTH)

AF:

0.0543

AC:

115

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

392

784

1177

1569

1961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0202

Hom.:

Bravo

AF:

0.0513

Asia WGS

AF:

0.0370

AC:

130

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.4

(source)

DANN

Benign

0.55

PhyloP100

-1.4

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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