rs9658134

Positions:

• chr6-35411021-G-A
• chr6-35411021-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.-67G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,383,208 control chromosomes in the GnomAD database, including 143 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 (18 hom., cov: 32)
  • Exomes 𝑓: 0.013 (125 hom.)
• Consequence: PPARD NM_006238.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-0.7).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1958/152234) while in subpopulation AFR AF= 0.0188 (780/41518). AF 95% confidence interval is 0.0177. There are 18 homozygotes in gnomad4. There are 844 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1958 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-67G>A		5_prime_UTR_variant	3/8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694	c.-67G>A		5_prime_UTR_variant	3/8	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1956 AN: 152116 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0134 AC: 16466 AN: 1230974 Hom.: 125 Cov.: 33 AF XY: 0.0130 AC XY: 7806 AN XY: 598482

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.00419

Gnomad4 ASJ exome AF: 0.000244

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000205

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.00992

GnomAD4 genome AF: 0.0129 AC: 1958 AN: 152234 Hom.: 18 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74424

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0123 Hom.: 18

Bravo AF: 0.0133

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9658134; hg19: chr6-35378798;