rs135539

Positions:

• chr22-46163368-A-C

Variant summary

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

The NM_005036.6(PPARA):​c.-127+11398A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,094 control chromosomes in the GnomAD database, including 21,140 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 0.51 (21140 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARA	NM_005036.6	c.-127+11398A>C		intron_variant		ENST00000407236.6	NP_005027.2
LOC105373074	XR_938315.3	n.128-2046T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.-127+11398A>C		intron_variant		1	NM_005036.6	ENSP00000385523	P1
	ENST00000624818.1	n.66A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77895 AN: 151976 Hom.: 21113 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.471

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.513 AC: 77973 AN: 152094 Hom.: 21140 Cov.: 32 AF XY: 0.509 AC XY: 37844 AN XY: 74346

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.465

Alfa AF: 0.473 Hom.: 3507

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs135539; hg19: chr22-46559267;