chr6-35424010-C-T

Variant names:

• chr6-35424010-C-T
• rs2076167
• NM_006238.5:c.489C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006238.5(PPARD):​c.489C>T​(p.Asn163Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 1,613,924 control chromosomes in the GnomAD database, including 465,387 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 0.68 (37006 hom., cov: 32)
  • Exomes 𝑓: 0.76 (428381 hom.)
• Consequence: PPARD NM_006238.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-2.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.489C>T	p.Asn163Asn	synonymous_variant	Exon 6 of 8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.489C>T	p.Asn163Asn	synonymous_variant	Exon 6 of 8	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103155 AN: 151972 Hom.: 36993 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.660

GnomAD3 exomes AF: 0.755 AC: 189795 AN: 251416 Hom.: 73189 AF XY: 0.760 AC XY: 103289 AN XY: 135888

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.714

Gnomad SAS exome AF: 0.786

Gnomad FIN exome AF: 0.891

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.762 AC: 1114382 AN: 1461834 Hom.: 428381 Cov.: 68 AF XY: 0.763 AC XY: 554960 AN XY: 727222

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.723

GnomAD4 genome AF: 0.678 AC: 103193 AN: 152090 Hom.: 37006 Cov.: 32 AF XY: 0.686 AC XY: 51004 AN XY: 74368

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.661

Alfa AF: 0.739 Hom.: 85592

Bravo AF: 0.653

Asia WGS AF: 0.713 AC: 2476 AN: 3478

EpiCase AF: 0.759

EpiControl AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2076167; hg19: chr6-35391787;