rs5767700

Positions:

• chr22-46216775-T-C
• chr22-46216775-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.369+1442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,158 control chromosomes in the GnomAD database, including 4,741 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 0.24 (4741 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.369+1442T>C		intron_variant		ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.369+1442T>C		intron_variant		1	NM_005036.6	P1
PPARA	ENST00000402126.1	c.369+1442T>C		intron_variant		1		P1
PPARA	ENST00000493286.1	n.579+1442T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37065 AN: 152040 Hom.: 4735 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.244 AC: 37097 AN: 152158 Hom.: 4741 Cov.: 32 AF XY: 0.242 AC XY: 17975 AN XY: 74384

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.240

Alfa AF: 0.196 Hom.: 2045

Bravo AF: 0.257

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.80

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: rs5767700; hg19: chr22-46612672;