rs4253765

Variant names:

• chr22-46226991-C-T
• rs4253765
• NM_005036.6:c.712-4801C>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.712-4801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,344 control chromosomes in the GnomAD database, including 7,878 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 0.27 (7878 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.712-4801C>T		intron_variant	Intron 7 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.712-4801C>T		intron_variant	Intron 7 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.712-4801C>T		intron_variant	Intron 6 of 7	1		ENSP00000385246.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40845 AN: 151230 Hom.: 7853 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.270 AC: 40903 AN: 151344 Hom.: 7878 Cov.: 32 AF XY: 0.262 AC XY: 19354 AN XY: 73986

African (AFR) AF: 0.545 AC: 22397 AN: 41074

American (AMR) AF: 0.180 AC: 2740 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.0814 AC: 391 AN: 4804

European-Finnish (FIN) AF: 0.138 AC: 1451 AN: 10528

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12517 AN: 67802

Other (OTH) AF: 0.234 AC: 490 AN: 2098

Alfa AF: 0.211 Hom.: 5329

Bravo AF: 0.287

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.29
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4253765; hg19: chr22-46622888;