6-35372523-C-T

Variant names:

• chr6-35372523-C-T
• rs12173582
• NM_006238.5:c.-102+25373C>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.-102+25373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,300 control chromosomes in the GnomAD database, including 376 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 0.043 (376 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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]

ENSG00000297330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-102+25373C>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.-102+25373C>T		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6519 AN: 152182 Hom.: 377 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0428 AC: 6513 AN: 152300 Hom.: 376 Cov.: 32 AF XY: 0.0475 AC XY: 3534 AN XY: 74474

African (AFR) AF: 0.0381 AC: 1585 AN: 41570

American (AMR) AF: 0.0509 AC: 778 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1574 AN: 5178

South Asian (SAS) AF: 0.115 AC: 556 AN: 4818

European-Finnish (FIN) AF: 0.0376 AC: 399 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1257 AN: 68034

Other (OTH) AF: 0.0488 AC: 103 AN: 2112

Alfa AF: 0.0252 Hom.: 130

Bravo AF: 0.0454

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		-0.086
Mutation Taster		=97/3	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: rs12173582; hg19: chr6-35340300;