chr6-35428227-T-G

Position:

• chr6-35428227-T-G

Variant summary

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

The 6-35428227-T-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,300 control chromosomes in the GnomAD database, including 56,550 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 0.86 (56550 hom., cov: 34)
  • Exomes 𝑓: 0.89 (61 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPARD NM_006238.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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 = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5			downstream_gene_variant		ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8			downstream_gene_variant		2	NM_006238.5	P1
PPARD	ENST00000311565.4			downstream_gene_variant		5		P1
PPARD	ENST00000418635.6			downstream_gene_variant		2
PPARD	ENST00000448077.6			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130944 AN: 152182 Hom.: 56494 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.853

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.895 AC: 136 AN: 152 Hom.: 61 Cov.: 0 AF XY: 0.888 AC XY: 87 AN XY: 98

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.861 AC: 131058 AN: 152300 Hom.: 56550 Cov.: 34 AF XY: 0.862 AC XY: 64166 AN XY: 74460

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.852

Alfa AF: 0.842 Hom.: 51015

Bravo AF: 0.859

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs760783; hg19: chr6-35396004;