6-35411001-C-T

Position:

• chr6-35411001-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.-87C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.797 in 1,328,196 control chromosomes in the GnomAD database, including 423,052 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 0.78 (46325 hom., cov: 31)
  • Exomes 𝑓: 0.80 (376727 hom.)
• Consequence: PPARD NM_006238.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-87C>T		5_prime_UTR_variant	3/8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694	c.-87C>T		5_prime_UTR_variant	3/8	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118226 AN: 151928 Hom.: 46288 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.800 AC: 940333 AN: 1176150 Hom.: 376727 Cov.: 59 AF XY: 0.800 AC XY: 452401 AN XY: 565850

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.805

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.778 AC: 118316 AN: 152046 Hom.: 46325 Cov.: 31 AF XY: 0.780 AC XY: 57986 AN XY: 74318

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.748

Alfa AF: 0.796 Hom.: 72000

Bravo AF: 0.767

Asia WGS AF: 0.747 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2016520; hg19: chr6-35378778; COSMIC: COSV61101982;