6-35424010-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	NM_006238.5	MANE Select	c.489C>T	p.Asn163Asn	synonymous	Exon 6 of 8	NP_006229.1	Q03181-1
	PPARD	NM_001171818.2		c.489C>T	p.Asn163Asn	synonymous	Exon 7 of 9	NP_001165289.1	Q03181-1
	PPARD	NM_001171819.2		c.372C>T	p.Asn124Asn	synonymous	Exon 5 of 7	NP_001165290.1	Q03181-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	ENST00000360694.8	TSL:2 MANE Select	c.489C>T	p.Asn163Asn	synonymous	Exon 6 of 8	ENSP00000353916.3	Q03181-1
	PPARD	ENST00000311565.4	TSL:5	c.489C>T	p.Asn163Asn	synonymous	Exon 7 of 9	ENSP00000310928.4	Q03181-1
	PPARD	ENST00000875334.1		c.489C>T	p.Asn163Asn	synonymous	Exon 5 of 7	ENSP00000545393.1

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

GnomAD2 exomes AF: 0.755 AC: 189795 AN: 251416 AF XY: 0.760

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 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

African (AFR) AF: 0.428 AC: 14342 AN: 33478

American (AMR) AF: 0.799 AC: 35725 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 14762 AN: 26136

East Asian (EAS) AF: 0.752 AC: 29848 AN: 39700

South Asian (SAS) AF: 0.784 AC: 67614 AN: 86256

European-Finnish (FIN) AF: 0.893 AC: 47698 AN: 53408

Middle Eastern (MID) AF: 0.617 AC: 3559 AN: 5768

European-Non Finnish (NFE) AF: 0.771 AC: 857182 AN: 1111978

Other (OTH) AF: 0.723 AC: 43652 AN: 60388

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

African (AFR) AF: 0.436 AC: 18060 AN: 41438

American (AMR) AF: 0.725 AC: 11088 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1963 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3713 AN: 5160

South Asian (SAS) AF: 0.794 AC: 3825 AN: 4820

European-Finnish (FIN) AF: 0.894 AC: 9484 AN: 10606

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.776 AC: 52780 AN: 67988

Other (OTH) AF: 0.661 AC: 1397 AN: 2112

Alfa AF: 0.725 Hom.: 132326

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.52
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076167; hg19: chr6-35391787; COSMIC: COSV100283016;