rs4253763

chr22-46226703-T-Cchr22-46226703-T-G

Variant summary

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

The NM_005036.6(PPARA):c.712-5089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,056 control chromosomes in the GnomAD database, including 1,112 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 0.10 (1112 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.712-5089T>C		intron_variant		ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.712-5089T>C		intron_variant		1	NM_005036.6	P1
PPARA	ENST00000402126.1	c.712-5089T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15190 AN: 151938 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.100 AC: 15223 AN: 152056 Hom.: 1112 Cov.: 32 AF XY: 0.0966 AC XY: 7178 AN XY: 74340

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0704

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0620 Hom.: 317

Bravo AF: 0.108

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.20
Dann	Benign	0.74

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: rs4253763; hg19: chr22-46622600;