rs12330015

Positions:

• chr22-46194381-A-G

Variant summary

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

The NM_005036.6(PPARA):​c.-42-3961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,166 control chromosomes in the GnomAD database, including 1,690 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 0.14 (1690 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARA	NM_005036.6	c.-42-3961A>G		intron_variant		ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.-42-3961A>G		intron_variant		1	NM_005036.6	ENSP00000385523	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21328 AN: 152048 Hom.: 1689 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.140 AC: 21355 AN: 152166 Hom.: 1690 Cov.: 32 AF XY: 0.140 AC XY: 10408 AN XY: 74390

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0974

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.143

Alfa AF: 0.113 Hom.: 1488

Bravo AF: 0.151

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.60

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: rs12330015; hg19: chr22-46590278;