6-35427841-C-T

Position:

• chr6-35427841-C-T

Variant summary

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

The NM_006238.5(PPARD):​c.*1762C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,818 control chromosomes in the GnomAD database, including 36,048 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 0.66 (35823 hom., cov: 34)
  • Exomes 𝑓: 0.85 (225 hom.)
• Consequence: PPARD NM_006238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632

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).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARD	NM_006238.5	c.*1762C>T		3_prime_UTR_variant	8/8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.*1762C>T		3_prime_UTR_variant	8/8	2	NM_006238.5	ENSP00000353916	P1
PPARD	ENST00000311565.4	c.*1762C>T		3_prime_UTR_variant	9/9	5		ENSP00000310928	P1
PPARD	ENST00000418635.6	c.*1762C>T		3_prime_UTR_variant	6/6	2		ENSP00000413314
PPARD	ENST00000448077.6	c.*1762C>T		3_prime_UTR_variant	7/7	2		ENSP00000414372

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100605 AN: 152074 Hom.: 35807 Cov.: 34

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.848 AC: 531 AN: 626 Hom.: 225 Cov.: 0 AF XY: 0.853 AC XY: 353 AN XY: 414

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.866

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.661 AC: 100640 AN: 152192 Hom.: 35823 Cov.: 34 AF XY: 0.669 AC XY: 49802 AN XY: 74416

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.645

Alfa AF: 0.744 Hom.: 62014

Bravo AF: 0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.49

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: rs1053049; hg19: chr6-35395618;