dbSNP rs9615264: PPARA:c.*1312G>A (chr22-46236692-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.*1312G>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 0.057 in 152,732 control chromosomes in the GnomAD database, including 337 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 0.057 ( 336 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1 hom. )

Consequence

PPARA
NM_005036.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.121

Publications

19 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6 link	c.*1312G>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.*1312G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_005036.6	ENSP00000385523.1		Q07869-1

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8693

AN:

152196

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0647

Gnomad FIN

AF:

0.0619

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.0588

GnomAD4 exome

AF:

0.0478

AC:

AN:

418

Hom.:

Cov.:

AF XY:

0.0543

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0493

AC:

AN:

406

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0570

AC:

8689

AN:

152314

Hom.:

336

Cov.:

AF XY:

0.0562

AC XY:

4185

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0148

AC:

615

AN:

41570

American (AMR)

AF:

0.0546

AC:

835

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0643

AC:

310

AN:

4820

European-Finnish (FIN)

AF:

0.0619

AC:

657

AN:

10618

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0854

AC:

5808

AN:

68030

Other (OTH)

AF:

0.0577

AC:

122

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0734

Hom.:

1005

Bravo

AF:

0.0521

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.60

PhyloP100

-0.12

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