6-35365964-G-C

Variant names:

• chr6-35365964-G-C
• rs9470001
• NM_006238.5:c.-102+18814G>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+18814G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,582 control chromosomes in the GnomAD database, including 8,853 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 (8853 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-102+18814G>C		intron_variant	Intron 2 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.-102+18814G>C		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33891 AN: 151466 Hom.: 8813 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.224 AC: 33985 AN: 151582 Hom.: 8853 Cov.: 32 AF XY: 0.217 AC XY: 16071 AN XY: 74120

African (AFR) AF: 0.621 AC: 25366 AN: 40874

American (AMR) AF: 0.143 AC: 2188 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3470

East Asian (EAS) AF: 0.0273 AC: 142 AN: 5192

South Asian (SAS) AF: 0.0640 AC: 309 AN: 4828

European-Finnish (FIN) AF: 0.0218 AC: 232 AN: 10628

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4542 AN: 68020

Other (OTH) AF: 0.219 AC: 461 AN: 2104

Alfa AF: 0.154 Hom.: 645

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.94
DANN	Benign	0.51
PhyloP100		-0.15
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: rs9470001; hg19: chr6-35333741;