4-158723349-C-T

Position:

• chr4-158723349-C-T

Variant summary

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

The NM_005038.3(PPID):​c.-61G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,517,194 control chromosomes in the GnomAD database, including 65,337 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 0.27 (5911 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59426 hom.)
• Consequence: PPID NM_005038.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

Genes affected

PPID (HGNC:9257): (peptidylprolyl isomerase D) 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 has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPID	NM_005038.3	c.-61G>A		5_prime_UTR_variant	1/10	ENST00000307720.4	NP_005029.1
PPID	XM_047415844.1	c.-61G>A		5_prime_UTR_variant	1/5		XP_047271800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPID	ENST00000307720.4	c.-61G>A		5_prime_UTR_variant	1/10	1	NM_005038.3	ENSP00000303754.3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41598 AN: 151874 Hom.: 5905 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.291 AC: 397796 AN: 1365202 Hom.: 59426 Cov.: 22 AF XY: 0.292 AC XY: 199604 AN XY: 682820

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.274 AC: 41621 AN: 151992 Hom.: 5911 Cov.: 32 AF XY: 0.267 AC XY: 19821 AN XY: 74270

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.268

Alfa AF: 0.232 Hom.: 1277

Bravo AF: 0.270

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2070629; hg19: chr4-159644501; COSMIC: COSV56987555;