6-35404747-G-C

Variant names:

• chr6-35404747-G-C
• rs2267667
• NM_006238.5:c.-101-6240G>C

Variant summary

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

The NM_006238.5(PPARD):​c.-101-6240G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,100 control chromosomes in the GnomAD database, including 34,932 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 0.65 (34932 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-101-6240G>C		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.-101-6240G>C		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99265 AN: 151982 Hom.: 34919 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.653 AC: 99297 AN: 152100 Hom.: 34932 Cov.: 32 AF XY: 0.660 AC XY: 49096 AN XY: 74380

African (AFR) AF: 0.376 AC: 15593 AN: 41480

American (AMR) AF: 0.719 AC: 10976 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3674 AN: 5162

South Asian (SAS) AF: 0.787 AC: 3797 AN: 4826

European-Finnish (FIN) AF: 0.865 AC: 9171 AN: 10600

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51880 AN: 67972

Other (OTH) AF: 0.645 AC: 1360 AN: 2108

Alfa AF: 0.660 Hom.: 2569

Bravo AF: 0.628

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2
DANN	Benign	0.75
PhyloP100		0.42
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: rs2267667; hg19: chr6-35372524;