rs4253772

chr22-46231706-C-T

Variant summary

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

The NM_005036.6(PPARA):c.712-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,377,132 control chromosomes in the GnomAD database, including 7,188 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 0.077 (590 hom., cov: 32)
  • Exomes 𝑓: 0.098 (6598 hom.)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.712-86C>T		intron_variant		ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.712-86C>T		intron_variant		1	NM_005036.6	P1
PPARA	ENST00000402126.1	c.712-86C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11752 AN: 152130 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0984 AC: 120547 AN: 1224882 Hom.: 6598 AF XY: 0.0978 AC XY: 60046 AN XY: 613822

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.0576

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.000332

Gnomad4 SAS exome AF: 0.0677

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.0926

GnomAD4 genome AF: 0.0772 AC: 11749 AN: 152250 Hom.: 590 Cov.: 32 AF XY: 0.0748 AC XY: 5570 AN XY: 74432

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0801

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0552

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.103 Hom.: 1822

Bravo AF: 0.0748

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.045
Dann	Benign	0.68

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: rs4253772; hg19: chr22-46627603;