rs6008259

Positions:

• chr22-46237885-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.*2505G>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 0.309 in 152,270 control chromosomes in the GnomAD database, including 11,469 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 0.31 (11468 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: PPARA NM_005036.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.*2505G>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.*2505G>A		3_prime_UTR_variant	9/9	1	NM_005036.6	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46975 AN: 152068 Hom.: 11430 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.155 AC: 13 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.191 AC XY: 13 AN XY: 68

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.309 AC: 47053 AN: 152186 Hom.: 11468 Cov.: 32 AF XY: 0.300 AC XY: 22292 AN XY: 74408

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.260

Alfa AF: 0.187 Hom.: 3218

Bravo AF: 0.329

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.43

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: rs6008259; hg19: chr22-46633782;