rs6457816

Variant names:

• chr6-35395071-T-C
• rs6457816
• NM_006238.5:c.-101-15916T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006238.5(PPARD):​c.-101-15916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,054 control chromosomes in the GnomAD database, including 7,778 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 0.22 (7778 hom., cov: 31)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 22 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 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.-101-15916T>C		intron	N/A	NP_006229.1	Q03181-1
	PPARD	NM_001171818.2		c.-197-2427T>C		intron	N/A	NP_001165289.1	Q03181-1
	PPARD	NM_001171819.2		c.14-25056T>C		intron	N/A	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.-101-15916T>C		intron	N/A	ENSP00000353916.3	Q03181-1
	PPARD	ENST00000311565.4	TSL:5	c.-197-2427T>C		intron	N/A	ENSP00000310928.4	Q03181-1
	PPARD	ENST00000875334.1		c.-101-15916T>C		intron	N/A	ENSP00000545393.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33307 AN: 151936 Hom.: 7737 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33397 AN: 152054 Hom.: 7778 Cov.: 31 AF XY: 0.212 AC XY: 15758 AN XY: 74370

African (AFR) AF: 0.585 AC: 24228 AN: 41388

American (AMR) AF: 0.152 AC: 2322 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3466

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5176

South Asian (SAS) AF: 0.0674 AC: 325 AN: 4824

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10612

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4773 AN: 67988

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.126 Hom.: 10250

Bravo AF: 0.249

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.63
Mutation Taster		=100/0	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: rs6457816; hg19: chr6-35362848;