dbSNP rs135539: PPARA:c.-127+11398A>C (chr22-46163368-A-C) – 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.-127+11398A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,094 control chromosomes in the GnomAD database, including 21,140 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 0.51 ( 21140 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PPARA
NM_005036.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250

Publications

31 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:

ENSG00000280384 (HGNC:):

ENSG00000280384 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARA	NM_005036.6	MANE Select	c.-127+11398A>C	intron	N/A	NP_005027.2
PPARA	NM_001001928.4		c.-43+11398A>C	intron	N/A	NP_001001928.1	Q07869-1
PPARA	NM_001362872.2		c.-124+11398A>C	intron	N/A	NP_001349801.1	Q07869-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARA	ENST00000407236.6	TSL:1 MANE Select	c.-127+11398A>C	intron	N/A	ENSP00000385523.1	Q07869-1
PPARA	ENST00000402126.2	TSL:1	c.-124+11398A>C	intron	N/A	ENSP00000385246.1	Q07869-1
PPARA	ENST00000440343.5	TSL:1	c.-127+11398A>C	intron	N/A	ENSP00000397291.1	Q86SF0

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77895

AN:

151976

Hom.:

21113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.471

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.513

AC:

77973

AN:

152094

Hom.:

21140

Cov.:

AF XY:

0.509

AC XY:

37844

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.702

AC:

29121

AN:

41492

American (AMR)

AF:

0.448

AC:

6854

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1042

AN:

3470

East Asian (EAS)

AF:

0.527

AC:

2726

AN:

5176

South Asian (SAS)

AF:

0.419

AC:

2017

AN:

4812

European-Finnish (FIN)

AF:

0.455

AC:

4821

AN:

10586

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29846

AN:

67960

Other (OTH)

AF:

0.465

AC:

981

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1867

3733

5600

7466

9333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.473

Hom.:

3507

Bravo

AF:

0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

4.8

(source)

PhyloP100

-0.025

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over