22-46159422-C-T

Variant names:

• chr22-46159422-C-T
• rs135543
• NM_005036.6:c.-127+7452C>T

Variant summary

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

The NM_005036.6(PPARA):​c.-127+7452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,964 control chromosomes in the GnomAD database, including 6,018 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 0.28 (6018 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	NM_005036.6	MANE Select	c.-127+7452C>T		intron	N/A	NP_005027.2
	PPARA	NM_001001928.4		c.-43+7452C>T		intron	N/A	NP_001001928.1	Q07869-1
	PPARA	NM_001362872.2		c.-124+7452C>T		intron	N/A	NP_001349801.1	Q07869-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	ENST00000407236.6	TSL:1 MANE Select	c.-127+7452C>T		intron	N/A	ENSP00000385523.1	Q07869-1
	PPARA	ENST00000402126.2	TSL:1	c.-124+7452C>T		intron	N/A	ENSP00000385246.1	Q07869-1
	PPARA	ENST00000440343.5	TSL:1	c.-127+7452C>T		intron	N/A	ENSP00000397291.1	Q86SF0

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41796 AN: 151846 Hom.: 6010 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.275 AC: 41839 AN: 151964 Hom.: 6018 Cov.: 32 AF XY: 0.271 AC XY: 20144 AN XY: 74262

African (AFR) AF: 0.264 AC: 10921 AN: 41424

American (AMR) AF: 0.235 AC: 3586 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 748 AN: 3472

East Asian (EAS) AF: 0.0791 AC: 409 AN: 5168

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4820

European-Finnish (FIN) AF: 0.290 AC: 3065 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20914 AN: 67970

Other (OTH) AF: 0.280 AC: 588 AN: 2100

Alfa AF: 0.291 Hom.: 17129

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.055
PhyloP100		-4.0

Splicing

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

Other links and lift over

dbSNP: rs135543; hg19: chr22-46555321;