6-35422222-G-T

Variant names:

• chr6-35422222-G-T
• rs2076168
• NM_006238.5:c.424+264G>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.424+264G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,086 control chromosomes in the GnomAD database, including 38,049 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 0.69 (38049 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.424+264G>T		intron_variant	Intron 5 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.424+264G>T		intron_variant	Intron 5 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104861 AN: 151968 Hom.: 38035 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.690 AC: 104902 AN: 152086 Hom.: 38049 Cov.: 32 AF XY: 0.697 AC XY: 51826 AN XY: 74376

African (AFR) AF: 0.453 AC: 18791 AN: 41442

American (AMR) AF: 0.739 AC: 11297 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3720 AN: 5172

South Asian (SAS) AF: 0.807 AC: 3889 AN: 4822

European-Finnish (FIN) AF: 0.903 AC: 9568 AN: 10600

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53305 AN: 67978

Other (OTH) AF: 0.673 AC: 1419 AN: 2110

Alfa AF: 0.703 Hom.: 2378

Bravo AF: 0.676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.9
DANN	Benign	0.60
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2076168; hg19: chr6-35389999;