chr22-46154203-A-G

Variant names:

• chr22-46154203-A-G
• rs4253623
• NM_005036.6:c.-127+2233A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005036.6(PPARA):​c.-127+2233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,268 control chromosomes in the GnomAD database, including 1,069 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 0.11 (1069 hom., cov: 32)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 26 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.-127+2233A>G		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+2233A>G		intron_variant	Intron 2 of 8	1	NM_005036.6	ENSP00000385523.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17023 AN: 152150 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.112 AC: 17024 AN: 152268 Hom.: 1069 Cov.: 32 AF XY: 0.112 AC XY: 8358 AN XY: 74446

African (AFR) AF: 0.0570 AC: 2370 AN: 41560

American (AMR) AF: 0.112 AC: 1718 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 267 AN: 3468

East Asian (EAS) AF: 0.118 AC: 609 AN: 5182

South Asian (SAS) AF: 0.154 AC: 744 AN: 4828

European-Finnish (FIN) AF: 0.141 AC: 1496 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9526 AN: 68016

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.129 Hom.: 2263

Bravo AF: 0.107

Asia WGS AF: 0.128 AC: 444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -1

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

Other links and lift over

dbSNP: rs4253623; hg19: chr22-46550106;