dbSNP rs3768026: PPIH:c.243+191C>A (chr1-42661095-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006347.4(PPIH):c.243+191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 560,250 control chromosomes in the GnomAD database, including 28,881 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 0.31 ( 7450 hom., cov: 32)

Exomes 𝑓: 0.31 ( 21431 hom. )

Consequence

PPIH
NM_006347.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

1 publications found

Variant links:

Genes affected

PPIH (HGNC:14651): (peptidylprolyl isomerase H) The protein encoded by this gene is 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. This protein is a specific component of the complex that includes pre-mRNA processing factors PRPF3, PRPF4, and PRPF18, as well as U4/U5/U6 tri-snRNP. This protein has been shown to possess PPIase activity and may act as a protein chaperone that mediates the interactions between different proteins inside the spliceosome. [provided by RefSeq, Jul 2008]

PPIH links:

ENSG00000285728 (HGNC:):

ENSG00000285728 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIH	NM_006347.4 link	c.243+191C>A		intron_variant	Intron 5 of 9	ENST00000304979.8	NP_006338.1	O43447-1Q6FH36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIH	ENST00000304979.8 link	c.243+191C>A		intron_variant	Intron 5 of 9	1	NM_006347.4	ENSP00000306614.3		O43447-1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47143

AN:

151886

Hom.:

7448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.315

AC:

128399

AN:

408246

Hom.:

21431

AF XY:

0.315

AC XY:

68196

AN XY:

216420

show subpopulations

African (AFR)

AF:

0.284

AC:

2958

AN:

10408

American (AMR)

AF:

0.297

AC:

4108

AN:

13816

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

3620

AN:

12460

East Asian (EAS)

AF:

0.0964

AC:

2669

AN:

27692

South Asian (SAS)

AF:

0.333

AC:

12563

AN:

37672

European-Finnish (FIN)

AF:

0.410

AC:

12272

AN:

29906

Middle Eastern (MID)

AF:

0.307

AC:

1068

AN:

3484

European-Non Finnish (NFE)

AF:

0.328

AC:

81766

AN:

248914

Other (OTH)

AF:

0.309

AC:

7375

AN:

23894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4015

8031

12046

16062

20077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.310

AC:

47154

AN:

152004

Hom.:

7450

Cov.:

AF XY:

0.315

AC XY:

23364

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.287

AC:

11894

AN:

41434

American (AMR)

AF:

0.299

AC:

4571

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

966

AN:

3470

East Asian (EAS)

AF:

0.141

AC:

729

AN:

5168

South Asian (SAS)

AF:

0.315

AC:

1518

AN:

4820

European-Finnish (FIN)

AF:

0.411

AC:

4331

AN:

10548

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.328

AC:

22264

AN:

67970

Other (OTH)

AF:

0.307

AC:

648

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1683

3365

5048

6730

8413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.218

Hom.:

527

Bravo

AF:

0.299

Asia WGS

AF:

0.214

AC:

747

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.7

(source)

DANN

Benign

0.69

PhyloP100

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