6-35428227-T-G

Variant names:

• chr6-35428227-T-G
• rs760783
• NM_006238.5:c.*2148T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006238.5(PPARD):​c.*2148T>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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	NM_006238.5	MANE Select	c.*2148T>G		downstream_gene	N/A	NP_006229.1
	PPARD	NM_001171818.2		c.*2148T>G		downstream_gene	N/A	NP_001165289.1
	PPARD	NM_001171819.2		c.*2148T>G		downstream_gene	N/A	NP_001165290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	ENST00000360694.8	TSL:2 MANE Select	c.*2148T>G		downstream_gene	N/A	ENSP00000353916.3
	PPARD	ENST00000311565.4	TSL:5	c.*2148T>G		downstream_gene	N/A	ENSP00000310928.4
	PPARD	ENST00000448077.6	TSL:2	c.*2148T>G		downstream_gene	N/A	ENSP00000414372.2

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.902 AC: 110 AN: 122

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 21 AN: 24

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.894 AC: 37139 AN: 41564

American (AMR) AF: 0.862 AC: 13188 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2686 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3842 AN: 5176

South Asian (SAS) AF: 0.858 AC: 4136 AN: 4822

European-Finnish (FIN) AF: 0.916 AC: 9733 AN: 10620

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57545 AN: 68032

Other (OTH) AF: 0.852 AC: 1802 AN: 2114

Alfa AF: 0.850 Hom.: 74797

Bravo AF: 0.859

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.32
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760783; hg19: chr6-35396004;