rs9380506

Variant names:

• chr6-35399113-A-C
• rs9380506
• NM_006238.5:c.-101-11874A>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.-101-11874A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 149,910 control chromosomes in the GnomAD database, including 694 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 0.083 (694 hom., cov: 31)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-101-11874A>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.-101-11874A>C		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12411 AN: 149794 Hom.: 693 Cov.: 31

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0464

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0686

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0859

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

GnomAD4 genome AF: 0.0828 AC: 12416 AN: 149910 Hom.: 694 Cov.: 31 AF XY: 0.0844 AC XY: 6181 AN XY: 73194

African (AFR) AF: 0.0216 AC: 877 AN: 40538

American (AMR) AF: 0.0889 AC: 1339 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 279 AN: 3450

East Asian (EAS) AF: 0.255 AC: 1295 AN: 5080

South Asian (SAS) AF: 0.133 AC: 628 AN: 4718

European-Finnish (FIN) AF: 0.0930 AC: 956 AN: 10278

Middle Eastern (MID) AF: 0.0664 AC: 19 AN: 286

European-Non Finnish (NFE) AF: 0.101 AC: 6799 AN: 67518

Other (OTH) AF: 0.0878 AC: 182 AN: 2074

Alfa AF: 0.0837 Hom.: 76

Bravo AF: 0.0765

Asia WGS AF: 0.183 AC: 638 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		0.34
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: rs9380506; hg19: chr6-35366890;