chr6-35402029-C-T

Variant names:

• chr6-35402029-C-T
• rs1883322
• NM_006238.5:c.-101-8958C>T

Variant summary

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

The NM_006238.5(PPARD):​c.-101-8958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,964 control chromosomes in the GnomAD database, including 35,760 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 0.67 (35760 hom., cov: 30)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 25 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=-0.8).
• 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.-101-8958C>T		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.-101-8958C>T		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101343 AN: 151846 Hom.: 35748 Cov.: 30

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.667 AC: 101378 AN: 151964 Hom.: 35760 Cov.: 30 AF XY: 0.674 AC XY: 50050 AN XY: 74270

African (AFR) AF: 0.424 AC: 17549 AN: 41398

American (AMR) AF: 0.725 AC: 11073 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1978 AN: 3466

East Asian (EAS) AF: 0.712 AC: 3654 AN: 5134

South Asian (SAS) AF: 0.787 AC: 3795 AN: 4820

European-Finnish (FIN) AF: 0.865 AC: 9148 AN: 10578

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51925 AN: 67974

Other (OTH) AF: 0.658 AC: 1389 AN: 2110

Alfa AF: 0.718 Hom.: 123085

Bravo AF: 0.644

Asia WGS AF: 0.707 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.013
Mutation Taster		=99/1	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: rs1883322; hg19: chr6-35369806;