chr22-46231706-C-T

Variant names:

• chr22-46231706-C-T
• rs4253772
• NM_005036.6:c.712-86C>T

Variant summary

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

The NM_005036.6(PPARA):​c.712-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,377,132 control chromosomes in the GnomAD database, including 7,188 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 0.077 (590 hom., cov: 32)
  • Exomes 𝑓: 0.098 (6598 hom.)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 65 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.712-86C>T		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.712-86C>T		intron_variant	Intron 7 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.712-86C>T		intron_variant	Intron 6 of 7	1		ENSP00000385246.1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11752 AN: 152130 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0984 AC: 120547 AN: 1224882 Hom.: 6598 AF XY: 0.0978 AC XY: 60046 AN XY: 613822

African (AFR) AF: 0.0229 AC: 651 AN: 28416

American (AMR) AF: 0.0576 AC: 2103 AN: 36488

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2903 AN: 24150

East Asian (EAS) AF: 0.000332 AC: 12 AN: 36130

South Asian (SAS) AF: 0.0677 AC: 5143 AN: 75928

European-Finnish (FIN) AF: 0.0765 AC: 3768 AN: 49246

Middle Eastern (MID) AF: 0.0908 AC: 340 AN: 3746

European-Non Finnish (NFE) AF: 0.110 AC: 100769 AN: 918330

Other (OTH) AF: 0.0926 AC: 4858 AN: 52448

GnomAD4 genome AF: 0.0772 AC: 11749 AN: 152250 Hom.: 590 Cov.: 32 AF XY: 0.0748 AC XY: 5570 AN XY: 74432

African (AFR) AF: 0.0249 AC: 1035 AN: 41542

American (AMR) AF: 0.0801 AC: 1224 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4818

European-Finnish (FIN) AF: 0.0754 AC: 799 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7603 AN: 68036

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0968 Hom.: 2488

Bravo AF: 0.0748

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.68
PhyloP100		-3.3
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: rs4253772; hg19: chr22-46627603;