NM_006238.5:c.*1939G>C

Variant names:

• chr6-35428018-G-C
• rs9794
• NM_006238.5:c.*1939G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006238.5(PPARD):​c.*1939G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,648 control chromosomes in the GnomAD database, including 55,060 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 0.85 (54900 hom., cov: 32)
  • Exomes 𝑓: 0.88 (160 hom.)
• Consequence: PPARD NM_006238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 35 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.*1939G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.*1939G>C		3_prime_UTR_variant	Exon 8 of 8	2	NM_006238.5	ENSP00000353916.3
PPARD	ENST00000311565.4	c.*1939G>C		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000310928.4
PPARD	ENST00000448077.6	c.*1939G>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000414372.2
PPARD	ENST00000418635.6	c.*1939G>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000413314.2

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128988 AN: 152112 Hom.: 54849 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.876 AC: 366 AN: 418 Hom.: 160 Cov.: 0 AF XY: 0.885 AC XY: 230 AN XY: 260

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.889 AC: 343 AN: 386

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.708 AC: 17 AN: 24

Other (OTH) AF: 1.00 AC: 2 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.848 AC: 129097 AN: 152230 Hom.: 54900 Cov.: 32 AF XY: 0.850 AC XY: 63227 AN XY: 74416

African (AFR) AF: 0.876 AC: 36372 AN: 41542

American (AMR) AF: 0.848 AC: 12973 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2624 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3806 AN: 5148

South Asian (SAS) AF: 0.842 AC: 4059 AN: 4822

European-Finnish (FIN) AF: 0.908 AC: 9631 AN: 10610

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56876 AN: 68014

Other (OTH) AF: 0.840 AC: 1777 AN: 2116

Alfa AF: 0.847 Hom.: 2584

Bravo AF: 0.859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.69
PhyloP100		-1.9
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: rs9794; hg19: chr6-35395795; COSMIC: COSV61098571; COSMIC: COSV61098571;