rs2267664

Positions:

• chr6-35344477-G-A
• chr6-35344477-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006238.5(PPARD):​c.-186+1796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 151,888 control chromosomes in the GnomAD database, including 379 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 0.043 (379 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5	c.-186+1796G>A		intron_variant		ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.-186+1796G>A		intron_variant		2	NM_006238.5	P1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6522 AN: 151770 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0509

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

GnomAD4 genome AF: 0.0429 AC: 6521 AN: 151888 Hom.: 379 Cov.: 32 AF XY: 0.0476 AC XY: 3530 AN XY: 74188

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0257 Hom.: 147

Bravo AF: 0.0455

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.78

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: rs2267664; hg19: chr6-35312254;