22-46226487-T-G

Variant names:

• chr22-46226487-T-G
• rs4253760
• NM_005036.6:c.712-5305T>G

Variant summary

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

The NM_005036.6(PPARA):​c.712-5305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,120 control chromosomes in the GnomAD database, including 11,783 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 0.32 (11783 hom., cov: 33)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 16 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.712-5305T>G		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.712-5305T>G		intron_variant	Intron 7 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.712-5305T>G		intron_variant	Intron 6 of 7	1		ENSP00000385246.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47841 AN: 152002 Hom.: 11741 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.315 AC: 47927 AN: 152120 Hom.: 11783 Cov.: 33 AF XY: 0.306 AC XY: 22790 AN XY: 74414

African (AFR) AF: 0.687 AC: 28487 AN: 41452

American (AMR) AF: 0.196 AC: 2998 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3464

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5194

South Asian (SAS) AF: 0.0862 AC: 416 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10604

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12769 AN: 67980

Other (OTH) AF: 0.267 AC: 566 AN: 2116

Alfa AF: 0.236 Hom.: 9327

Bravo AF: 0.334

Asia WGS AF: 0.0860 AC: 301 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	1.6
DANN	Benign	0.52
PhyloP100		0.011
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: rs4253760; hg19: chr22-46622384;