22-46166284-T-C

Variant names:

• chr22-46166284-T-C
• rs9626730
• NM_005036.6:c.-126-10469T>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.-126-10469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,016 control chromosomes in the GnomAD database, including 3,525 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 0.20 (3525 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 7 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]

ENSG00000310070 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.338 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	NM_005036.6	MANE Select	c.-126-10469T>C		intron	N/A	NP_005027.2
	PPARA	NM_001001928.4		c.-43+14314T>C		intron	N/A	NP_001001928.1
	PPARA	NM_001362872.2		c.-123-10469T>C		intron	N/A	NP_001349801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	ENST00000407236.6	TSL:1 MANE Select	c.-126-10469T>C		intron	N/A	ENSP00000385523.1
	PPARA	ENST00000402126.2	TSL:1	c.-123-10469T>C		intron	N/A	ENSP00000385246.1
	PPARA	ENST00000440343.5	TSL:1	c.-126-10469T>C		intron	N/A	ENSP00000397291.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29691 AN: 151898 Hom.: 3522 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.196 AC: 29731 AN: 152016 Hom.: 3525 Cov.: 32 AF XY: 0.193 AC XY: 14315 AN XY: 74344

African (AFR) AF: 0.343 AC: 14202 AN: 41400

American (AMR) AF: 0.152 AC: 2328 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0892 AC: 309 AN: 3464

East Asian (EAS) AF: 0.125 AC: 648 AN: 5164

South Asian (SAS) AF: 0.152 AC: 731 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10584

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9616 AN: 67988

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.168 Hom.: 4081

Bravo AF: 0.203

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.72
PhyloP100		0.031
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: rs9626730; hg19: chr22-46562183;