rs3734254

Positions:

• chr6-35427233-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPARD	NM_006238.5	c.*1154C>T		3_prime_UTR_variant	8/8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.*1154C>T		3_prime_UTR_variant	8/8	2	NM_006238.5	ENSP00000353916	P1
PPARD	ENST00000311565.4	c.*1154C>T		3_prime_UTR_variant	9/9	5		ENSP00000310928	P1
PPARD	ENST00000418635.6	c.*1154C>T		3_prime_UTR_variant	6/6	2		ENSP00000413314
PPARD	ENST00000448077.6	c.*1154C>T		3_prime_UTR_variant	7/7	2		ENSP00000414372

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105812 AN: 151944 Hom.: 38907 Cov.: 32

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.: 0 AF XY: 0.764 AC XY: 3665 AN XY: 4798

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.783

Gnomad4 FIN exome AF: 0.908

Gnomad4 NFE exome AF: 0.769

Gnomad4 OTH exome AF: 0.712

GnomAD4 genome AF: 0.696 AC: 105853 AN: 152064 Hom.: 38922 Cov.: 32 AF XY: 0.702 AC XY: 52197 AN XY: 74316

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.682

Alfa AF: 0.773 Hom.: 64513

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

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

Other links and lift over

dbSNP: rs3734254; hg19: chr6-35395010;