6-35362644-T-C

Variant names:

• chr6-35362644-T-C
• rs6902123
• NM_006238.5:c.-102+15494T>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-102+15494T>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+15494T>C		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

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

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0275

Gnomad4 SAS AF: 0.0645

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.229

Alfa AF: 0.123 Hom.: 1146

Bravo AF: 0.264

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs6902123; hg19: chr6-35330421;