dbSNP rs6008259: PPARA:c.*2505G>A (chr22-46237885-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005036.6(PPARA):c.*2505G>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 0.309 in 152,270 control chromosomes in the GnomAD database, including 11,469 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 0.31 ( 11468 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

PPARA
NM_005036.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.12

Publications

22 publications found

Variant links:

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]

PPARA links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6 link	c.*2505G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000407236.6	NP_005027.2	Q07869-1F1D8S4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6 link	c.*2505G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_005036.6	ENSP00000385523.1		Q07869-1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46975

AN:

152068

Hom.:

11430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0871

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.263

GnomAD4 exome

AF:

0.155

AC:

AN:

Hom.:

Cov.:

AF XY:

0.191

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.177

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.309

AC:

47053

AN:

152186

Hom.:

11468

Cov.:

AF XY:

0.300

AC XY:

22292

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.680

AC:

28224

AN:

41492

American (AMR)

AF:

0.192

AC:

2937

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

551

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.0857

AC:

414

AN:

4830

European-Finnish (FIN)

AF:

0.139

AC:

1473

AN:

10600

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12588

AN:

68014

Other (OTH)

AF:

0.260

AC:

550

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1259

2519

3778

5038

6297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

7608

Bravo

AF:

0.329

Asia WGS

AF:

0.0820

AC:

288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.24

(source)

DANN

Benign

0.43

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over