rs6922548

Variant names:

• chr6-35385746-A-G
• rs6922548
• NM_006238.5:c.-101-25241A>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.-101-25241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,342 control chromosomes in the GnomAD database, including 8,730 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 0.23 (8730 hom., cov: 29)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 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.-101-25241A>G		intron	N/A	NP_006229.1
	PPARD	NM_001171818.2		c.-197-11752A>G		intron	N/A	NP_001165289.1
	PPARD	NM_001171819.2		c.14-34381A>G		intron	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.-101-25241A>G		intron	N/A	ENSP00000353916.3
	PPARD	ENST00000311565.4	TSL:5	c.-197-11752A>G		intron	N/A	ENSP00000310928.4
	PPARD	ENST00000448077.6	TSL:2	c.14-34381A>G		intron	N/A	ENSP00000414372.2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34475 AN: 151250 Hom.: 8694 Cov.: 29

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.228 AC: 34561 AN: 151342 Hom.: 8730 Cov.: 29 AF XY: 0.221 AC XY: 16348 AN XY: 73852

African (AFR) AF: 0.629 AC: 25889 AN: 41188

American (AMR) AF: 0.144 AC: 2195 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 643 AN: 3464

East Asian (EAS) AF: 0.0277 AC: 143 AN: 5162

South Asian (SAS) AF: 0.0645 AC: 308 AN: 4776

European-Finnish (FIN) AF: 0.0220 AC: 228 AN: 10356

Middle Eastern (MID) AF: 0.206 AC: 59 AN: 286

European-Non Finnish (NFE) AF: 0.0674 AC: 4577 AN: 67884

Other (OTH) AF: 0.226 AC: 476 AN: 2102

Alfa AF: 0.133 Hom.: 9463

Bravo AF: 0.260

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.4
DANN	Benign	0.66
PhyloP100		-0.034
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: rs6922548; hg19: chr6-35353523;