chr22-46242314-G-A

Variant names:

• chr22-46242314-G-A
• rs79700435
• NM_005036.6:c.*6934G>A

Variant summary

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

The NM_005036.6(PPARA):​c.*6934G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,620 control chromosomes in the GnomAD database, including 818 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 0.099 (815 hom., cov: 32)
  • Exomes 𝑓: 0.095 (3 hom.)
• Consequence: PPARA NM_005036.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	NM_005036.6	MANE Select	c.*6934G>A		3_prime_UTR	Exon 9 of 9	NP_005027.2
	PPARA	NM_001001928.4		c.*6934G>A		3_prime_UTR	Exon 8 of 8	NP_001001928.1	Q07869-1
	PPARA	NM_001001929.3		c.*6934G>A		3_prime_UTR	Exon 7 of 7	NP_001001929.1	Q07869-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	ENST00000407236.6	TSL:1 MANE Select	c.*6934G>A		3_prime_UTR	Exon 9 of 9	ENSP00000385523.1	Q07869-1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15045 AN: 152060 Hom.: 814 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0990

GnomAD4 exome AF: 0.0950 AC: 42 AN: 442 Hom.: 3 Cov.: 0 AF XY: 0.102 AC XY: 27 AN XY: 266

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0930 AC: 40 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.0990 AC: 15061 AN: 152178 Hom.: 815 Cov.: 32 AF XY: 0.0960 AC XY: 7144 AN XY: 74396

African (AFR) AF: 0.0996 AC: 4133 AN: 41496

American (AMR) AF: 0.0884 AC: 1352 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3464

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4830

European-Finnish (FIN) AF: 0.0759 AC: 804 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7657 AN: 68002

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.106 Hom.: 814

Bravo AF: 0.0988

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.59
PhyloP100		1.0
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: rs79700435; hg19: chr22-46638211;