6-35428018-G-C

Position:

• chr6-35428018-G-C

Variant summary

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

The NM_006238.5(PPARD):​c.*1939G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,648 control chromosomes in the GnomAD database, including 55,060 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 0.85 (54900 hom., cov: 32)
  • Exomes 𝑓: 0.88 (160 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARD	NM_006238.5	c.*1939G>C		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.*1939G>C		3_prime_UTR_variant	8/8	2	NM_006238.5	ENSP00000353916.3
PPARD	ENST00000311565.4	c.*1939G>C		3_prime_UTR_variant	9/9	5		ENSP00000310928.4
PPARD	ENST00000448077.6	c.*1939G>C		3_prime_UTR_variant	7/7	2		ENSP00000414372.2
PPARD	ENST00000418635.6	c.*1939G>C		3_prime_UTR_variant	6/6	2		ENSP00000413314.2

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128988 AN: 152112 Hom.: 54849 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.876 AC: 366 AN: 418 Hom.: 160 Cov.: 0 AF XY: 0.885 AC XY: 230 AN XY: 260

Gnomad4 AFR exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.889

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.848 AC: 129097 AN: 152230 Hom.: 54900 Cov.: 32 AF XY: 0.850 AC XY: 63227 AN XY: 74416

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.840

Alfa AF: 0.847 Hom.: 2584

Bravo AF: 0.859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.69

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; COSMIC: COSV61098571; COSMIC: COSV61098571;