6-35406684-A-G

Position:

• chr6-35406684-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006238.5(PPARD):​c.-101-4303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,746 control chromosomes in the GnomAD database, including 36,557 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 0.68 (36557 hom., cov: 30)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5	c.-101-4303A>G		intron_variant		ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.-101-4303A>G		intron_variant		2	NM_006238.5	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102578 AN: 151626 Hom.: 36544 Cov.: 30

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.676 AC: 102619 AN: 151746 Hom.: 36557 Cov.: 30 AF XY: 0.683 AC XY: 50606 AN XY: 74126

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.665

Alfa AF: 0.747 Hom.: 56366

Bravo AF: 0.654

Asia WGS AF: 0.722 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2038068; hg19: chr6-35374461;