rs4253712

Variant names:

• chr22-46199138-A-G
• rs4253712
• NM_005036.6:c.208+547A>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.208+547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,924 control chromosomes in the GnomAD database, including 5,643 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 0.26 (5643 hom., cov: 31)
• Consequence: PPARA NM_005036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.208+547A>G		intron_variant	Intron 4 of 8	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.208+547A>G		intron_variant	Intron 4 of 8	1	NM_005036.6	ENSP00000385523.1
PPARA	ENST00000402126.2	c.208+547A>G		intron_variant	Intron 3 of 7	1		ENSP00000385246.1
PPARA	ENST00000493286.1	n.418+547A>G		intron_variant	Intron 3 of 5	1
PPARA	ENST00000420804.5	c.208+547A>G		intron_variant	Intron 3 of 3	2		ENSP00000414752.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40172 AN: 151806 Hom.: 5628 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.265 AC: 40230 AN: 151924 Hom.: 5643 Cov.: 31 AF XY: 0.260 AC XY: 19300 AN XY: 74258

African (AFR) AF: 0.365 AC: 15130 AN: 41456

American (AMR) AF: 0.312 AC: 4759 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3468

East Asian (EAS) AF: 0.140 AC: 721 AN: 5158

South Asian (SAS) AF: 0.145 AC: 699 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1773 AN: 10562

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15463 AN: 67900

Other (OTH) AF: 0.257 AC: 541 AN: 2108

Alfa AF: 0.237 Hom.: 14897

Bravo AF: 0.282

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.33
PhyloP100		-0.056
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: rs4253712; hg19: chr22-46595035;