chr7-44800017-C-T

Position:

• chr7-44800017-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIA	NM_021130.5	c.362+143C>T		intron_variant		ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.182+143C>T		intron_variant			NP_001287910.1
PPIA	XM_047420536.1	c.182+143C>T		intron_variant			XP_047276492.1
PPIA	XM_047420537.1	c.182+143C>T		intron_variant			XP_047276493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6	c.362+143C>T		intron_variant		1	NM_021130.5	ENSP00000419425.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97414 AN: 152048 Hom.: 35534 Cov.: 33

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.: 9 AF XY: 0.759 AC XY: 272461 AN XY: 358966

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.867

Gnomad4 NFE exome AF: 0.829

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.640 AC: 97436 AN: 152166 Hom.: 35534 Cov.: 33 AF XY: 0.637 AC XY: 47392 AN XY: 74384

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.677

Alfa AF: 0.775 Hom.: 45915

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
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6463247; hg19: chr7-44839616; COSMIC: COSV63533969; COSMIC: COSV63533969;