rs9638978

Variant names:

• chr7-44800738-G-A
• rs9638978
• NM_021130.5:c.363-549G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021130.5(PPIA):​c.363-549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 151,952 control chromosomes in the GnomAD database, including 532 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 0.050 (532 hom., cov: 32)
• Consequence: PPIA NM_021130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 3 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIA	NM_021130.5	c.363-549G>A		intron_variant	Intron 4 of 4	ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.183-549G>A		intron_variant	Intron 5 of 5		NP_001287910.1
PPIA	XM_047420536.1	c.183-549G>A		intron_variant	Intron 5 of 5		XP_047276492.1
PPIA	XM_047420537.1	c.183-549G>A		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	c.363-549G>A		intron_variant	Intron 4 of 4	1	NM_021130.5	ENSP00000419425.1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7588 AN: 151832 Hom.: 529 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0500 AC: 7590 AN: 151952 Hom.: 532 Cov.: 32 AF XY: 0.0543 AC XY: 4036 AN XY: 74268

African (AFR) AF: 0.0118 AC: 488 AN: 41468

American (AMR) AF: 0.0850 AC: 1294 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1748 AN: 5122

South Asian (SAS) AF: 0.181 AC: 872 AN: 4812

European-Finnish (FIN) AF: 0.0406 AC: 430 AN: 10584

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2427 AN: 67958

Other (OTH) AF: 0.0528 AC: 111 AN: 2104

Alfa AF: 0.0415 Hom.: 302

Bravo AF: 0.0511

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.21
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9638978; hg19: chr7-44840337;