rs135551

Variant names:

• chr22-46157126-G-A
• rs135551
• NM_005036.6:c.-127+5156G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-46157126-G-A
• chr22-46157126-G-C
• chr22-46157126-G-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.-127+5156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,074 control chromosomes in the GnomAD database, including 10,300 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 0.34 (10300 hom., cov: 33)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.40
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.-127+5156G>A		intron_variant	Intron 2 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.-127+5156G>A		intron_variant	Intron 2 of 8	1	NM_005036.6	ENSP00000385523.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51045 AN: 151956 Hom.: 10284 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.336 AC: 51109 AN: 152074 Hom.: 10300 Cov.: 33 AF XY: 0.327 AC XY: 24299 AN XY: 74326

African (AFR) AF: 0.557 AC: 23112 AN: 41472

American (AMR) AF: 0.219 AC: 3344 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3472

East Asian (EAS) AF: 0.0793 AC: 411 AN: 5186

South Asian (SAS) AF: 0.169 AC: 816 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2636 AN: 10562

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

European-Non Finnish (NFE) AF: 0.280 AC: 19031 AN: 67964

Other (OTH) AF: 0.310 AC: 654 AN: 2108

Alfa AF: 0.292 Hom.: 23393

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
PhyloP100		-6.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs135551; hg19: chr22-46553021;