NM_006238.5:c.-87C>A

Variant names:

• chr6-35411001-C-A
• rs2016520
• NM_006238.5:c.-87C>A

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_006238.5(PPARD):c.-87C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPARD NM_006238.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 78 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006238.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PPARD NM_006238.5	MANE Select	c.-87C>A	5_prime_UTR	Exon 3 of 8	Prot: NP_006229.1 UniProt:
	PPARD NM_001171818.2		c.-87C>A	5_prime_UTR	Exon 4 of 9	Prot: NP_001165289.1 UniProt:
	PPARD NM_177435.3		c.-87C>A	5_prime_UTR	Exon 3 of 7	Prot: NP_803184.1 UniProt:

PPARD NM_006238.5

MANE Select

HGVSc / HGVSpc.-87C>A

Exon rankExon 3 of 8

5_prime_UTR

Prot: NP_006229.1UniProt: Q03181-1

PPARD NM_001171818.2

HGVSc / HGVSpc.-87C>A

Exon rankExon 4 of 9

5_prime_UTR

Prot: NP_001165289.1UniProt: Q03181-1

PPARD NM_177435.3

HGVSc / HGVSpc.-87C>A

Exon rankExon 3 of 7

5_prime_UTR

Prot: NP_803184.1UniProt: Q03181-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PPARD ENST00000360694.8	TSL:2MANE Select	c.-87C>A	5_prime_UTR	Exon 3 of 8	Prot: ENSP00000353916.3 UniProt:
	PPARD ENST00000311565.4	TSL:5	c.-87C>A	5_prime_UTR	Exon 4 of 9	Prot: ENSP00000310928.4 UniProt:
	PPARD ENST00000875334.1		c.-87C>A	5_prime_UTR	Exon 2 of 7	Prot: ENSP00000545393.1 UniProt:

PPARD ENST00000360694.8

TSL:2MANE Select

HGVSc / HGVSpc.-87C>A

Exon rankExon 3 of 8

5_prime_UTR

Prot: ENSP00000353916.3UniProt: Q03181-1

PPARD ENST00000311565.4

TSL:5

HGVSc / HGVSpc.-87C>A

Exon rankExon 4 of 9

5_prime_UTR

Prot: ENSP00000310928.4UniProt: Q03181-1

PPARD ENST00000875334.1

HGVSc / HGVSpc.-87C>A

Exon rankExon 2 of 7

5_prime_UTR

Prot: ENSP00000545393.1UniProt: Q03181-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:59
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	17
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.77
GPN-Star LLR	N/A	-4.4
GPN-Star score	N/A	4.4
PhyloP100	Uncertain	4.3
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.0

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs2016520;

hg19: chr6-35378778;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar