NM_005036.6:c.-42-8799T>C

Variant names:

• chr22-46189543-T-C
• rs4253699
• NM_005036.6:c.-42-8799T>C

Variant summary

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

The NM_005036.6(PPARA):​c.-42-8799T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,162 control chromosomes in the GnomAD database, including 4,144 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 0.22 (4144 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.31
• Publications: 3 publications found

Genes affected

PPARA (HGNC:9232): (peroxisome proliferator activated receptor alpha) Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	NM_005036.6	MANE Select	c.-42-8799T>C		intron	N/A	NP_005027.2
	PPARA	NM_001001928.4		c.-42-8799T>C		intron	N/A	NP_001001928.1
	PPARA	NM_001001929.3		c.-42-8799T>C		intron	N/A	NP_001001929.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	ENST00000407236.6	TSL:1 MANE Select	c.-42-8799T>C		intron	N/A	ENSP00000385523.1
	PPARA	ENST00000402126.2	TSL:1	c.-39-8802T>C		intron	N/A	ENSP00000385246.1
	PPARA	ENST00000440343.5	TSL:1	c.-42-8799T>C		intron	N/A	ENSP00000397291.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33772 AN: 152044 Hom.: 4124 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.222 AC: 33836 AN: 152162 Hom.: 4144 Cov.: 32 AF XY: 0.215 AC XY: 15972 AN XY: 74410

African (AFR) AF: 0.321 AC: 13317 AN: 41498

American (AMR) AF: 0.170 AC: 2600 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3466

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5188

South Asian (SAS) AF: 0.118 AC: 567 AN: 4824

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10602

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13925 AN: 67984

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.219 Hom.: 4661

Bravo AF: 0.229

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0030
DANN	Benign	0.43
PhyloP100		-5.3
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: rs4253699; hg19: chr22-46585440;