rs3734254

Variant names:

• chr6-35427233-C-T
• rs3734254
• NM_006238.5:c.*1154C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 publications found

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

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	c.*1154C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000360694.8	NP_006229.1

Ensembl

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

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

African (AFR) AF: 0.347 AC: 82 AN: 236

American (AMR) AF: 0.716 AC: 106 AN: 148

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 137 AN: 236

East Asian (EAS) AF: 0.770 AC: 705 AN: 916

South Asian (SAS) AF: 0.783 AC: 47 AN: 60

European-Finnish (FIN) AF: 0.908 AC: 1090 AN: 1200

Middle Eastern (MID) AF: 0.550 AC: 22 AN: 40

European-Non Finnish (NFE) AF: 0.769 AC: 4367 AN: 5678

Other (OTH) AF: 0.712 AC: 333 AN: 468

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

African (AFR) AF: 0.447 AC: 18530 AN: 41466

American (AMR) AF: 0.740 AC: 11310 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2015 AN: 3472

East Asian (EAS) AF: 0.723 AC: 3714 AN: 5138

South Asian (SAS) AF: 0.798 AC: 3846 AN: 4820

European-Finnish (FIN) AF: 0.906 AC: 9618 AN: 10616

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54485 AN: 67950

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

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
PhyloP100		-1.8
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

Other links and lift over

dbSNP: rs3734254; hg19: chr6-35395010;