rs135549

chr22-46157413-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.-127+5443T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,860 control chromosomes in the GnomAD database, including 18,539 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 0.48 (18539 hom., cov: 31)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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 = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.-127+5443T>C		intron_variant		ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.-127+5443T>C		intron_variant		1	NM_005036.6	P1
PPARA	ENST00000440343.5	c.-127+5443T>C		intron_variant		1
PPARA	ENST00000415785.5	c.-140+5443T>C		intron_variant		4
PPARA	ENST00000420804.5	c.-43+5443T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72239 AN: 151742 Hom.: 18509 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.476 AC: 72327 AN: 151860 Hom.: 18539 Cov.: 31 AF XY: 0.469 AC XY: 34793 AN XY: 74196

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.445

Alfa AF: 0.431 Hom.: 20866

Bravo AF: 0.482

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs135549; hg19: chr22-46553308;