rs9658130

Positions:

• chr6-35410263-A-G
• chr6-35410263-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006238.5(PPARD):​c.-101-724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 152,256 control chromosomes in the GnomAD database, including 50 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 0.021 (50 hom., cov: 33)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3228/152256) while in subpopulation NFE AF= 0.0327 (2226/68006). AF 95% confidence interval is 0.0316. There are 50 homozygotes in gnomad4. There are 1488 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5	c.-101-724A>G		intron_variant		ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.-101-724A>G		intron_variant		2	NM_006238.5	P1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3232 AN: 152138 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0212 AC: 3228 AN: 152256 Hom.: 50 Cov.: 33 AF XY: 0.0200 AC XY: 1488 AN XY: 74462

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0301 Hom.: 78

Bravo AF: 0.0217

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.86

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: rs9658130; hg19: chr6-35378040;