rs4253730

Variant names:

• chr22-46214512-A-G
• rs4253730
• NM_005036.6:c.209-661A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005036.6(PPARA):​c.209-661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 130,370 control chromosomes in the GnomAD database, including 8,938 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 0.37 (8938 hom., cov: 21)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.209-661A>G		intron_variant	Intron 4 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.209-661A>G		intron_variant	Intron 4 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.209-661A>G		intron_variant	Intron 3 of 7	1		ENSP00000385246.1
PPARA	ENST00000493286.1	n.419-661A>G		intron_variant	Intron 3 of 5	1
PPARA	ENST00000420804.5	c.209-661A>G		intron_variant	Intron 3 of 3	2		ENSP00000414752.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 48330 AN: 130248 Hom.: 8914 Cov.: 21

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.371 AC: 48396 AN: 130370 Hom.: 8938 Cov.: 21 AF XY: 0.371 AC XY: 23259 AN XY: 62682

African (AFR) AF: 0.548 AC: 19822 AN: 36146

American (AMR) AF: 0.356 AC: 4452 AN: 12510

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1044 AN: 3162

East Asian (EAS) AF: 0.234 AC: 881 AN: 3764

South Asian (SAS) AF: 0.209 AC: 733 AN: 3510

European-Finnish (FIN) AF: 0.285 AC: 2157 AN: 7572

Middle Eastern (MID) AF: 0.414 AC: 91 AN: 220

European-Non Finnish (NFE) AF: 0.300 AC: 18270 AN: 60930

Other (OTH) AF: 0.373 AC: 657 AN: 1762

Alfa AF: 0.295 Hom.: 26325

Bravo AF: 0.355

Asia WGS AF: 0.216 AC: 749 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.058
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4253730; hg19: chr22-46610409;