rs6850

Positions:

• chr7-44796715-A-G
• chr7-44796715-A-T

Variant summary

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

The NM_021130.5(PPIA):​c.-10A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,608,180 control chromosomes in the GnomAD database, including 40,964 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 0.26 (7445 hom., cov: 34)
  • Exomes 𝑓: 0.17 (33519 hom.)
• Consequence: PPIA NM_021130.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIA	NM_021130.5	c.-10A>G		5_prime_UTR_variant	1/5	ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.-347A>G		5_prime_UTR_variant	1/6		NP_001287910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812	c.-10A>G		5_prime_UTR_variant	1/5	1	NM_021130.5	ENSP00000419425.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39629 AN: 152084 Hom.: 7436 Cov.: 34

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.256 AC: 63537 AN: 247874 Hom.: 12545 AF XY: 0.246 AC XY: 33134 AN XY: 134528

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.334

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.170 AC: 247878 AN: 1455982 Hom.: 33519 Cov.: 33 AF XY: 0.173 AC XY: 125074 AN XY: 724564

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.261 AC: 39677 AN: 152198 Hom.: 7445 Cov.: 34 AF XY: 0.266 AC XY: 19826 AN XY: 74414

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.248

Alfa AF: 0.196 Hom.: 1216

Bravo AF: 0.285

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.37
DANN	Benign	0.39
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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

LitVar

Other links and lift over

dbSNP: rs6850; hg19: chr7-44836314;