7-44796669-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 7-44796669-C-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIA	NM_021130.5			upstream_gene_variant		ENST00000468812.6
PPIA	NM_001300981.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIA	ENST00000468812.6			upstream_gene_variant		1	NM_021130.5	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7734 AN: 152220 Hom.: 260 Cov.: 34

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.: 27 AF XY: 0.0712 AC XY: 48089 AN XY: 675480

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0682

Gnomad4 ASJ exome AF: 0.0590

Gnomad4 EAS exome AF: 0.0230

Gnomad4 SAS exome AF: 0.0654

Gnomad4 FIN exome AF: 0.0317

Gnomad4 NFE exome AF: 0.0784

Gnomad4 OTH exome AF: 0.0679

GnomAD4 genome AF: 0.0508 AC: 7731 AN: 152334 Hom.: 260 Cov.: 34 AF XY: 0.0504 AC XY: 3753 AN XY: 74488

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0202 Hom.: 17

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
Dann	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8177826; hg19: chr7-44836268;