rs1053046

Positions:

• chr6-35427801-G-A
• chr6-35427801-G-C

Variant summary

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

The NM_006238.5(PPARD):​c.*1722G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,734 control chromosomes in the GnomAD database, including 4,737 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 0.17 (4736 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1 hom.)
• Consequence: PPARD NM_006238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5	c.*1722G>A		3_prime_UTR_variant	8/8	ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.*1722G>A		3_prime_UTR_variant	8/8	2	NM_006238.5	P1
PPARD	ENST00000311565.4	c.*1722G>A		3_prime_UTR_variant	9/9	5		P1
PPARD	ENST00000418635.6	c.*1722G>A		3_prime_UTR_variant	6/6	2
PPARD	ENST00000448077.6	c.*1722G>A		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25715 AN: 152100 Hom.: 4707 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.0370 AC: 19 AN: 514 Hom.: 1 Cov.: 0 AF XY: 0.0414 AC XY: 14 AN XY: 338

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0188

Gnomad4 NFE exome AF: 0.0614

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.169 AC: 25788 AN: 152220 Hom.: 4736 Cov.: 33 AF XY: 0.164 AC XY: 12238 AN XY: 74436

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0702 Hom.: 1254

Bravo AF: 0.193

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.71
DANN	Benign	0.62

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: rs1053046; hg19: chr6-35395578;