rs9615264

chr22-46236692-G-A

Variant summary

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

The NM_005036.6(PPARA):c.*1312G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 152,732 control chromosomes in the GnomAD database, including 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 0.057 (336 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1 hom.)
• Consequence: PPARA NM_005036.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

Genes affected

PPARA (HGNC:9232): (peroxisome proliferator activated receptor alpha) Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.*1312G>A		3_prime_UTR_variant	9/9	ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.*1312G>A		3_prime_UTR_variant	9/9	1	NM_005036.6	P1

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8693 AN: 152196 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0478 AC: 20 AN: 418 Hom.: 1 Cov.: 0 AF XY: 0.0543 AC XY: 14 AN XY: 258

Gnomad4 FIN exome AF: 0.0493

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0570 AC: 8689 AN: 152314 Hom.: 336 Cov.: 32 AF XY: 0.0562 AC XY: 4185 AN XY: 74488

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0643

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0769 Hom.: 715

Bravo AF: 0.0521

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.60

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: rs9615264; hg19: chr22-46632589;