6-35362644-T-C

Variant names:

• chr6-35362644-T-C
• rs6902123
• NM_006238.5:c.-102+15494T>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.-102+15494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,992 control chromosomes in the GnomAD database, including 9,057 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 0.23 (9057 hom., cov: 31)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 24 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]

ENSG00000297330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 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.-102+15494T>C		intron	N/A	NP_006229.1	Q03181-1
	PPARD	NM_001171818.2		c.-198+15494T>C		intron	N/A	NP_001165289.1	Q03181-1
	PPARD	NM_001171819.2		c.13+15494T>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.-102+15494T>C		intron	N/A	ENSP00000353916.3	Q03181-1
	PPARD	ENST00000311565.4	TSL:5	c.-198+15494T>C		intron	N/A	ENSP00000310928.4	Q03181-1
	PPARD	ENST00000875334.1		c.-102+19963T>C		intron	N/A	ENSP00000545393.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35085 AN: 151874 Hom.: 9015 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.231 AC: 35180 AN: 151992 Hom.: 9057 Cov.: 31 AF XY: 0.224 AC XY: 16657 AN XY: 74330

African (AFR) AF: 0.639 AC: 26415 AN: 41360

American (AMR) AF: 0.149 AC: 2275 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.0275 AC: 142 AN: 5166

South Asian (SAS) AF: 0.0645 AC: 311 AN: 4818

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10606

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4576 AN: 67980

Other (OTH) AF: 0.229 AC: 483 AN: 2108

Alfa AF: 0.139 Hom.: 1569

Bravo AF: 0.264

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.64
PhyloP100		0.18
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: rs6902123; hg19: chr6-35330421;