1-39722441-C-T

Position:

• chr1-39722441-C-T

Variant summary

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

The ENST00000470018.5(PPIE):​c.-325-13027C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,064 control chromosomes in the GnomAD database, including 25,668 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 0.58 (25668 hom., cov: 32)
• Consequence: PPIE ENST00000470018.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

PPIE (HGNC:9258): (peptidylprolyl isomerase E) 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 contains a highly conserved cyclophilin (CYP) domain as well as an RNA-binding domain. It was shown to possess PPIase and protein folding activities, and it also exhibits RNA-binding activity. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 1, has been identified. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIE	ENST00000470018.5	c.-325-13027C>T		intron_variant		5		ENSP00000436689

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87653 AN: 151946 Hom.: 25633 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.577 AC: 87746 AN: 152064 Hom.: 25668 Cov.: 32 AF XY: 0.578 AC XY: 42985 AN XY: 74316

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.551

Alfa AF: 0.548 Hom.: 38815

Bravo AF: 0.575

Asia WGS AF: 0.698 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs704784; hg19: chr1-40188113;