dbSNP rs6463247: PPIA:c.362+143C>T (chr7-44800017-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 NM_021130.5(PPIA):c.362+143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 851,794 control chromosomes in the GnomAD database, including 247,805 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 0.64 ( 35534 hom., cov: 33)

Exomes 𝑓: 0.76 ( 212271 hom. )

Consequence

PPIA
NM_021130.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0750

Publications

12 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPIA	NM_021130.5 link	c.362+143C>T	intron_variant	Intron 4 of 4	ENST00000468812.6	NP_066953.1	P62937-1V9HWF5
PPIA	NM_001300981.2 link	c.182+143C>T	intron_variant	Intron 5 of 5		NP_001287910.1	P62937-2
PPIA	XM_047420536.1 link	c.182+143C>T	intron_variant	Intron 5 of 5		XP_047276492.1
PPIA	XM_047420537.1 link	c.182+143C>T	intron_variant	Intron 5 of 5		XP_047276493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6 link	c.362+143C>T		intron_variant	Intron 4 of 4	1	NM_021130.5	ENSP00000419425.1		P62937-1

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97414

AN:

152048

Hom.:

35534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.867

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.678

GnomAD4 exome

AF:

0.761

AC:

532626

AN:

699628

Hom.:

212271

Cov.:

AF XY:

0.759

AC XY:

272461

AN XY:

358966

show subpopulations

African (AFR)

AF:

0.313

AC:

5424

AN:

17324

American (AMR)

AF:

0.563

AC:

11938

AN:

21190

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

13538

AN:

15786

East Asian (EAS)

AF:

0.201

AC:

6771

AN:

33622

South Asian (SAS)

AF:

0.643

AC:

33989

AN:

52848

European-Finnish (FIN)

AF:

0.867

AC:

27033

AN:

31194

Middle Eastern (MID)

AF:

0.736

AC:

2167

AN:

2946

European-Non Finnish (NFE)

AF:

0.829

AC:

406433

AN:

490298

Other (OTH)

AF:

0.736

AC:

25333

AN:

34420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5472

10944

16416

21888

27360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6136

12272

18408

24544

30680

<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:

0.640

AC:

97436

AN:

152166

Hom.:

35534

Cov.:

AF XY:

0.637

AC XY:

47392

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.320

AC:

13294

AN:

41520

American (AMR)

AF:

0.599

AC:

9147

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.845

AC:

2933

AN:

3470

East Asian (EAS)

AF:

0.233

AC:

1209

AN:

5178

South Asian (SAS)

AF:

0.628

AC:

3032

AN:

4828

European-Finnish (FIN)

AF:

0.867

AC:

9173

AN:

10582

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.828

AC:

56339

AN:

68002

Other (OTH)

AF:

0.677

AC:

1430

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1399

2798

4196

5595

6994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.754

Hom.:

57474

Bravo

AF:

0.604

Asia WGS

AF:

0.454

AC:

1577

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.0

(source)

DANN

Benign

0.36

PhyloP100

-0.075

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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