rs4253699

chr22-46189543-T-C

Variant summary

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

The NM_005036.6(PPARA):c.-42-8799T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,162 control chromosomes in the GnomAD database, including 4,144 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 0.22 (4144 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.31

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.-42-8799T>C		intron_variant		ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.-42-8799T>C		intron_variant		1	NM_005036.6	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33772 AN: 152044 Hom.: 4124 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33836 AN: 152162 Hom.: 4144 Cov.: 32 AF XY: 0.215 AC XY: 15972 AN XY: 74410

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.222

Alfa AF: 0.216 Hom.: 3371

Bravo AF: 0.229

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.0030
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: rs4253699; hg19: chr22-46585440;