rs4253778

Positions:

• chr22-46234737-G-C
• chr22-46234737-G-T

Variant summary

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

The NM_005036.6(PPARA):​c.1160-396G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,118 control chromosomes in the GnomAD database, including 11,585 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 (11585 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARA	NM_005036.6	c.1160-396G>C		intron_variant		ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.1160-396G>C		intron_variant		1	NM_005036.6	ENSP00000385523	P1
PPARA	ENST00000402126.1	c.1160-396G>C		intron_variant		1		ENSP00000385246	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47243 AN: 152000 Hom.: 11545 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.311 AC: 47324 AN: 152118 Hom.: 11585 Cov.: 32 AF XY: 0.301 AC XY: 22414 AN XY: 74394

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.263

Alfa AF: 0.111 Hom.: 174

Bravo AF: 0.331

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.34

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: rs4253778; hg19: chr22-46630634;