rs9794

chr6-35428018-G-Achr6-35428018-G-Cchr6-35428018-G-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.*1939G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 152,684 control chromosomes in the GnomAD database, including 13 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 0.013 (13 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: PPARD NM_006238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2025/152254) while in subpopulation AFR AF= 0.0248 (1029/41552). AF 95% confidence interval is 0.0235. There are 13 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2020 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5	c.*1939G>A		3_prime_UTR_variant	8/8	ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.*1939G>A		3_prime_UTR_variant	8/8	2	NM_006238.5	P1
PPARD	ENST00000311565.4	c.*1939G>A		3_prime_UTR_variant	9/9	5		P1
PPARD	ENST00000418635.6	c.*1939G>A		3_prime_UTR_variant	6/6	2
PPARD	ENST00000448077.6	c.*1939G>A		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2020 AN: 152136 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00839

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.0209 AC: 9 AN: 430 Hom.: 0 Cov.: 0 AF XY: 0.0222 AC XY: 6 AN XY: 270

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.0151

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0133 AC: 2025 AN: 152254 Hom.: 13 Cov.: 32 AF XY: 0.0131 AC XY: 975 AN XY: 74432

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00839

Gnomad4 NFE AF: 0.00775

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00217 Hom.: 2584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.027
Dann	Benign	0.93

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: rs9794; hg19: chr6-35395795;