dbSNP rs3734254: PPARD:c.*1154C>T (chr6-35427233-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.*1154C>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 0.7 in 161,046 control chromosomes in the GnomAD database, including 41,607 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 0.70 ( 38922 hom., cov: 32)

Exomes 𝑓: 0.77 ( 2685 hom. )

Consequence

PPARD
NM_006238.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76

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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5 link	c.*1154C>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.*1154C>T	3_prime_UTR_variant	Exon 8 of 8	2	NM_006238.5	ENSP00000353916.3	Q03181-1
PPARD	ENST00000311565.4 link	c.*1154C>T	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000310928.4	Q03181-1
PPARD	ENST00000448077.6 link	c.*1154C>T	3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000414372.2	Q03181-3
PPARD	ENST00000418635.6 link	c.*1154C>T	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000413314.2	Q03181-4

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105812

AN:

151944

Hom.:

38907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.799

Gnomad FIN

AF:

0.906

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.681

GnomAD4 exome

AF:

0.767

AC:

6889

AN:

8982

Hom.:

2685

Cov.:

AF XY:

0.764

AC XY:

3665

AN XY:

4798

show subpopulations

Gnomad4 AFR exome

AF:

0.347

AC:

AN:

236

Gnomad4 AMR exome

AF:

0.716

AC:

106

AN:

148

Gnomad4 ASJ exome

AF:

0.581

AC:

137

AN:

236

Gnomad4 EAS exome

AF:

0.770

AC:

705

AN:

916

Gnomad4 SAS exome

AF:

0.783

AC:

AN:

Gnomad4 FIN exome

AF:

0.908

AC:

1090

AN:

1200

Gnomad4 NFE exome

AF:

0.769

AC:

4367

AN:

5678

Gnomad4 Remaining exome

AF:

0.712

AC:

333

AN:

468

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<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:

0.696

AC:

105853

AN:

152064

Hom.:

38922

Cov.:

AF XY:

0.702

AC XY:

52197

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.447

AC:

0.446872

AN:

0.446872

Gnomad4 AMR

AF:

0.740

AC:

0.739893

AN:

0.739893

Gnomad4 ASJ

AF:

0.580

AC:

0.580357

AN:

0.580357

Gnomad4 EAS

AF:

0.723

AC:

0.722849

AN:

0.722849

Gnomad4 SAS

AF:

0.798

AC:

0.797925

AN:

0.797925

Gnomad4 FIN

AF:

0.906

AC:

0.905991

AN:

0.905991

Gnomad4 NFE

AF:

0.802

AC:

0.80184

AN:

0.80184

Gnomad4 OTH

AF:

0.682

AC:

0.682119

AN:

0.682119

Heterozygous variant carriers

1468

2936

4405

5873

7341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.759

Hom.:

148804

Bravo

AF:

0.671

Asia WGS

AF:

0.721

AC:

2504

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.052

DANN

Benign

0.59

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over