rs6906237

Variant names:

• chr6-35407749-C-A
• rs6906237
• NM_006238.5:c.-101-3238C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35407749-C-A
• chr6-35407749-C-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.-101-3238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 149,668 control chromosomes in the GnomAD database, including 4,642 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 0.17 (4642 hom., cov: 30)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-101-3238C>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.-101-3238C>A		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26062 AN: 149576 Hom.: 4623 Cov.: 30

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.174 AC: 26117 AN: 149668 Hom.: 4642 Cov.: 30 AF XY: 0.169 AC XY: 12308 AN XY: 73002

African (AFR) AF: 0.454 AC: 18540 AN: 40832

American (AMR) AF: 0.126 AC: 1892 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3462

East Asian (EAS) AF: 0.0196 AC: 101 AN: 5142

South Asian (SAS) AF: 0.0496 AC: 233 AN: 4694

European-Finnish (FIN) AF: 0.0126 AC: 123 AN: 9788

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.0605 AC: 4082 AN: 67430

Other (OTH) AF: 0.184 AC: 382 AN: 2080

Alfa AF: 0.0971 Hom.: 2819

Bravo AF: 0.197

Asia WGS AF: 0.0570 AC: 199 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.20
PhyloP100		-2.3
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: rs6906237; hg19: chr6-35375526;