rs2267669

Variant names:

• chr6-35410347-G-A
• rs2267669
• NM_006238.5:c.-101-640G>A

Variant summary

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

The NM_006238.5(PPARD):​c.-101-640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,214 control chromosomes in the GnomAD database, including 55,246 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 (55246 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-101-640G>A		intron_variant	Intron 2 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.-101-640G>A		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129410 AN: 152096 Hom.: 55193 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.851 AC: 129521 AN: 152214 Hom.: 55246 Cov.: 32 AF XY: 0.851 AC XY: 63350 AN XY: 74408

African (AFR) AF: 0.892 AC: 37026 AN: 41522

American (AMR) AF: 0.860 AC: 13146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2705 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3867 AN: 5184

South Asian (SAS) AF: 0.850 AC: 4094 AN: 4816

European-Finnish (FIN) AF: 0.887 AC: 9405 AN: 10608

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56510 AN: 68004

Other (OTH) AF: 0.848 AC: 1793 AN: 2114

Alfa AF: 0.834 Hom.: 98231

Bravo AF: 0.852

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.64
DANN	Benign	0.67
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2267669; hg19: chr6-35378124;