rs8396

chr4-158709665-T-C

Variant summary

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

The NM_005038.3(PPID):c.*71A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,195,066 control chromosomes in the GnomAD database, including 51,293 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 0.29 (6537 hom., cov: 32)
  • Exomes 𝑓: 0.29 (44756 hom.)
• Consequence: PPID NM_005038.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

ETFDH (HGNC:3483): (electron transfer flavoprotein dehydrogenase) This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPID	NM_005038.3	c.*71A>G		3_prime_UTR_variant	10/10	ENST00000307720.4
ETFDH	NM_004453.4			downstream_gene_variant		ENST00000511912.6
ETFDH	NM_001281737.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPID	ENST00000307720.4	c.*71A>G		3_prime_UTR_variant	10/10	1	NM_005038.3	P1
ETFDH	ENST00000511912.6			downstream_gene_variant		1	NM_004453.4	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43681 AN: 152024 Hom.: 6535 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.289 AC: 301892 AN: 1042926 Hom.: 44756 Cov.: 13 AF XY: 0.289 AC XY: 153762 AN XY: 531454

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.287 AC: 43704 AN: 152140 Hom.: 6537 Cov.: 32 AF XY: 0.280 AC XY: 20808 AN XY: 74398

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.275

Alfa AF: 0.287 Hom.: 11639

Bravo AF: 0.285

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.38
Dann	Benign	0.57
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: rs8396; hg19: chr4-159630817; COSMIC: COSV56987535; COSMIC: COSV56987535;