1-39722441-C-T

Variant names:

• chr1-39722441-C-T
• rs704784
• ENST00000470018.5:c.-325-13027C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIE	ENST00000470018.5	c.-325-13027C>T		intron_variant	Intron 1 of 7	5		ENSP00000436689.1

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;