NM_005036.6:c.712-5695T>C

Variant names:

• chr22-46226097-T-C
• rs5767743
• NM_005036.6:c.712-5695T>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.712-5695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,570 control chromosomes in the GnomAD database, including 12,806 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 0.35 (12806 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 15 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.712-5695T>C		intron_variant	Intron 7 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.712-5695T>C		intron_variant	Intron 7 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.712-5695T>C		intron_variant	Intron 6 of 7	1		ENSP00000385246.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53001 AN: 151450 Hom.: 12766 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.350 AC: 53083 AN: 151570 Hom.: 12806 Cov.: 32 AF XY: 0.351 AC XY: 25971 AN XY: 74064

African (AFR) AF: 0.690 AC: 28503 AN: 41310

American (AMR) AF: 0.282 AC: 4298 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3462

East Asian (EAS) AF: 0.236 AC: 1216 AN: 5142

South Asian (SAS) AF: 0.132 AC: 630 AN: 4788

European-Finnish (FIN) AF: 0.304 AC: 3187 AN: 10476

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13645 AN: 67844

Other (OTH) AF: 0.293 AC: 617 AN: 2106

Alfa AF: 0.237 Hom.: 7198

Bravo AF: 0.366

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.39
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs5767743; hg19: chr22-46621994; COSMIC: COSV53082215;