Genetic Variant PPARD:c.*1762C>T (chr6-35427841-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006238.5(PPARD):c.*1762C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,818 control chromosomes in the GnomAD database, including 36,048 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 0.66 ( 35823 hom., cov: 34)

Exomes 𝑓: 0.85 ( 225 hom. )

Consequence

PPARD
NM_006238.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.632

Publications

49 publications found

Variant links:

Genes affected

PPARD (HGNC:9235): (peroxisome proliferator activated receptor delta) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2017]

PPARD 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=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5 link	c.*1762C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000360694.8	NP_006229.1	Q03181-1A0A024RCW6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPARD	ENST00000360694.8 link	c.*1762C>T	3_prime_UTR_variant	Exon 8 of 8	2	NM_006238.5	ENSP00000353916.3	Q03181-1
PPARD	ENST00000311565.4 link	c.*1762C>T	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000310928.4	Q03181-1
PPARD	ENST00000448077.6 link	c.*1762C>T	3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000414372.2	Q03181-3
PPARD	ENST00000418635.6 link	c.*1762C>T	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000413314.2	Q03181-4

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100605

AN:

152074

Hom.:

35807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.848

AC:

531

AN:

626

Hom.:

225

Cov.:

AF XY:

0.853

AC XY:

353

AN XY:

414

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.866

AC:

367

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.812

AC:

138

AN:

170

Other (OTH)

AF:

0.900

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.661

AC:

100640

AN:

152192

Hom.:

35823

Cov.:

AF XY:

0.669

AC XY:

49802

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.387

AC:

16073

AN:

41520

American (AMR)

AF:

0.714

AC:

10918

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1962

AN:

3472

East Asian (EAS)

AF:

0.721

AC:

3717

AN:

5154

South Asian (SAS)

AF:

0.791

AC:

3823

AN:

4832

European-Finnish (FIN)

AF:

0.892

AC:

9472

AN:

10614

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52440

AN:

67988

Other (OTH)

AF:

0.645

AC:

1363

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1545

3090

4635

6180

7725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.718

Hom.:

93110

Bravo

AF:

0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

(source)

DANN

Benign

0.49

PhyloP100

0.63

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over