rs4253755

Variant names:

• chr22-46219479-G-A
• rs4253755
• NM_005036.6:c.509-333G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-46219479-G-A
• chr22-46219479-G-C

Variant summary

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

The NM_005036.6(PPARA):​c.509-333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,200 control chromosomes in the GnomAD database, including 717 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 0.086 (717 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.509-333G>A		intron_variant	Intron 6 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.509-333G>A		intron_variant	Intron 6 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.509-333G>A		intron_variant	Intron 5 of 7	1		ENSP00000385246.1
PPARA	ENST00000493286.1	n.719-333G>A		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13070 AN: 152082 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0858 AC: 13059 AN: 152200 Hom.: 717 Cov.: 32 AF XY: 0.0825 AC XY: 6142 AN XY: 74426

African (AFR) AF: 0.0221 AC: 917 AN: 41534

American (AMR) AF: 0.0823 AC: 1258 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4826

European-Finnish (FIN) AF: 0.0760 AC: 806 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8906 AN: 67982

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.114 Hom.: 1830

Bravo AF: 0.0833

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.62
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4253755; hg19: chr22-46615376;