6-35425627-A-G

Variant names:

• chr6-35425627-A-G
• rs2076166
• NM_006238.5:c.1079-205A>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.1079-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 151,908 control chromosomes in the GnomAD database, including 56,594 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 0.86 (56594 hom., cov: 29)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.1079-205A>G		intron_variant	Intron 7 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.1079-205A>G		intron_variant	Intron 7 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130805 AN: 151790 Hom.: 56541 Cov.: 29

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.862 AC: 130916 AN: 151908 Hom.: 56594 Cov.: 29 AF XY: 0.863 AC XY: 64083 AN XY: 74250

African (AFR) AF: 0.902 AC: 37325 AN: 41380

American (AMR) AF: 0.862 AC: 13168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3773 AN: 5120

South Asian (SAS) AF: 0.856 AC: 4122 AN: 4816

European-Finnish (FIN) AF: 0.916 AC: 9677 AN: 10564

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57371 AN: 67960

Other (OTH) AF: 0.853 AC: 1802 AN: 2112

Alfa AF: 0.848 Hom.: 51773

Bravo AF: 0.861

Asia WGS AF: 0.783 AC: 2724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.032
DANN	Benign	0.24
PhyloP100		-1.8
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: rs2076166; hg19: chr6-35393404;