6-35411001-C-T

Variant names:

• chr6-35411001-C-T
• rs2016520
• NM_006238.5:c.-87C>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.-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
• Publications: 202 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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 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.-87C>T		5_prime_UTR	Exon 3 of 8	NP_006229.1	Q03181-1
	PPARD	NM_001171818.2		c.-87C>T		5_prime_UTR	Exon 4 of 9	NP_001165289.1	Q03181-1
	PPARD	NM_177435.3		c.-87C>T		5_prime_UTR	Exon 3 of 7	NP_803184.1	Q03181-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	ENST00000360694.8	TSL:2 MANE Select	c.-87C>T		5_prime_UTR	Exon 3 of 8	ENSP00000353916.3	Q03181-1
	PPARD	ENST00000311565.4	TSL:5	c.-87C>T		5_prime_UTR	Exon 4 of 9	ENSP00000310928.4	Q03181-1
	PPARD	ENST00000875334.1		c.-87C>T		5_prime_UTR	Exon 2 of 7	ENSP00000545393.1

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

African (AFR) AF: 0.713 AC: 17857 AN: 25052

American (AMR) AF: 0.823 AC: 9598 AN: 11658

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 9526 AN: 15440

East Asian (EAS) AF: 0.765 AC: 22780 AN: 29774

South Asian (SAS) AF: 0.805 AC: 30878 AN: 38380

European-Finnish (FIN) AF: 0.884 AC: 37240 AN: 42114

Middle Eastern (MID) AF: 0.699 AC: 3285 AN: 4702

European-Non Finnish (NFE) AF: 0.803 AC: 772718 AN: 961712

Other (OTH) AF: 0.770 AC: 36451 AN: 47318

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

African (AFR) AF: 0.712 AC: 29535 AN: 41462

American (AMR) AF: 0.788 AC: 12036 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2157 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3718 AN: 5156

South Asian (SAS) AF: 0.807 AC: 3886 AN: 4816

European-Finnish (FIN) AF: 0.884 AC: 9360 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55095 AN: 67964

Other (OTH) AF: 0.748 AC: 1581 AN: 2114

Alfa AF: 0.794 Hom.: 164276

Bravo AF: 0.767

Asia WGS AF: 0.747 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.77
PhyloP100		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	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: rs2016520; hg19: chr6-35378778; COSMIC: COSV61101982;