NM_005036.6:c.711+821T>C

Variant names:

• chr22-46220835-T-C
• rs4253758
• NM_005036.6:c.711+821T>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.711+821T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,520 control chromosomes in the GnomAD database, including 18,461 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 0.42 (18461 hom., cov: 29)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 1 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.711+821T>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.711+821T>C		intron_variant	Intron 7 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.711+821T>C		intron_variant	Intron 6 of 7	1		ENSP00000385246.1
PPARA	ENST00000493286.1	n.*178T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63087 AN: 151400 Hom.: 18400 Cov.: 29

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.417 AC: 63192 AN: 151520 Hom.: 18461 Cov.: 29 AF XY: 0.411 AC XY: 30441 AN XY: 74030

African (AFR) AF: 0.841 AC: 34757 AN: 41318

American (AMR) AF: 0.328 AC: 4989 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3464

East Asian (EAS) AF: 0.279 AC: 1418 AN: 5078

South Asian (SAS) AF: 0.160 AC: 767 AN: 4802

European-Finnish (FIN) AF: 0.227 AC: 2385 AN: 10492

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16936 AN: 67852

Other (OTH) AF: 0.374 AC: 787 AN: 2102

Alfa AF: 0.325 Hom.: 1351

Bravo AF: 0.447

Asia WGS AF: 0.256 AC: 894 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	0.25
DANN	Benign	0.29
PhyloP100		-2.4
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: rs4253758; hg19: chr22-46616732;