rs3892755

Variant names:

• chr22-46239702-G-A
• rs3892755
• NM_005036.6:c.*4322G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-46239702-G-A
• chr22-46239702-G-C

Variant summary

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

The NM_005036.6(PPARA):​c.*4322G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.088 (1382 hom., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPARA NM_005036.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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.*4322G>A		3_prime_UTR	Exon 9 of 9	NP_005027.2
	PPARA	NM_001001928.4		c.*4322G>A		3_prime_UTR	Exon 8 of 8	NP_001001928.1	Q07869-1
	PPARA	NM_001001929.3		c.*4322G>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.*4322G>A		3_prime_UTR	Exon 9 of 9	ENSP00000385523.1	Q07869-1
	PPARA	ENST00000873468.1		c.*4322G>A		3_prime_UTR	Exon 8 of 8	ENSP00000543527.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 9792 AN: 111674 Hom.: 1384 Cov.: 19

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.000324

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000388

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0666

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0877 AC: 9802 AN: 111744 Hom.: 1382 Cov.: 19 AF XY: 0.0901 AC XY: 4578 AN XY: 50830

African (AFR) AF: 0.312 AC: 9264 AN: 29738

American (AMR) AF: 0.0455 AC: 363 AN: 7980

Ashkenazi Jewish (ASJ) AF: 0.000324 AC: 1 AN: 3088

East Asian (EAS) AF: 0.00 AC: 0 AN: 3346

South Asian (SAS) AF: 0.000388 AC: 1 AN: 2580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.00125 AC: 73 AN: 58444

Other (OTH) AF: 0.0659 AC: 100 AN: 1518

Alfa AF: 0.0305 Hom.: 1530

Bravo AF: 0.0954

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.58
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3892755;

hg19: chr22-46635599;