chr22-46242314-G-A

Position:

• chr22-46242314-G-A

Variant summary

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

The NM_005036.6(PPARA):​c.*6934G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,620 control chromosomes in the GnomAD database, including 818 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 0.099 (815 hom., cov: 32)
  • Exomes 𝑓: 0.095 (3 hom.)
• Consequence: PPARA NM_005036.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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 (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.*6934G>A		3_prime_UTR_variant	9/9	ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.*6934G>A		3_prime_UTR_variant	9/9	1	NM_005036.6	P1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15045 AN: 152060 Hom.: 814 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0990

GnomAD4 exome AF: 0.0950 AC: 42 AN: 442 Hom.: 3 Cov.: 0 AF XY: 0.102 AC XY: 27 AN XY: 266

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0990 AC: 15061 AN: 152178 Hom.: 815 Cov.: 32 AF XY: 0.0960 AC XY: 7144 AN XY: 74396

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.109 Hom.: 450

Bravo AF: 0.0988

Asia WGS AF: 0.0280 AC: 99 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	7.6
DANN	Benign	0.59

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: rs79700435; hg19: chr22-46638211;