rs1800206

chr22-46218377-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005036.6(PPARA):c.484C>G(p.Leu162Val) variant causes a missense change. The variant allele was found at a frequency of 0.0573 in 1,614,008 control chromosomes in the GnomAD database, including 3,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.042 (172 hom., cov: 30)
  • Exomes 𝑓: 0.059 (2922 hom.)
• Consequence: PPARA NM_005036.6 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.00

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00670588).
• BP6: Variant 22-46218377-C-G is Benign according to our data. Variant chr22-46218377-C-G is described in ClinVar as [Benign]. Clinvar id is 13701.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARA	NM_005036.6	c.484C>G	p.Leu162Val	missense_variant	6/9	ENST00000407236.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARA	ENST00000407236.6	c.484C>G	p.Leu162Val	missense_variant	6/9	1	NM_005036.6	P1
PPARA	ENST00000402126.1	c.484C>G	p.Leu162Val	missense_variant	4/7	1		P1
PPARA	ENST00000493286.1	n.694C>G		non_coding_transcript_exon_variant	5/6	1

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6425 AN: 152108 Hom.: 173 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0606

GnomAD3 exomes AF: 0.0434 AC: 10923 AN: 251492 Hom.: 316 AF XY: 0.0433 AC XY: 5889 AN XY: 135918

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.0402

Gnomad ASJ exome AF: 0.0429

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0245

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0626

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0588 AC: 86009 AN: 1461782 Hom.: 2922 Cov.: 32 AF XY: 0.0578 AC XY: 42060 AN XY: 727194

Gnomad4 AFR exome AF: 0.00923

Gnomad4 AMR exome AF: 0.0429

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0251

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.0677

Gnomad4 OTH exome AF: 0.0529

GnomAD4 genome AF: 0.0422 AC: 6417 AN: 152226 Hom.: 172 Cov.: 30 AF XY: 0.0399 AC XY: 2972 AN XY: 74414

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0569 Hom.: 84

Bravo AF: 0.0436

TwinsUK AF: 0.0680 AC: 252

ALSPAC AF: 0.0693 AC: 267

ESP6500AA AF: 0.0127 AC: 56

ESP6500EA AF: 0.0624 AC: 537

ExAC AF: 0.0425 AC: 5155

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.0678

EpiControl AF: 0.0649

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyperapobetalipoproteinemia, susceptibility to Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jan 01, 2004

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Pathogenic	0.40
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D;D
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;.;.
MetaRNN	Benign	0.0067	T;T;T
MetaSVM	Uncertain	0.056	D
MutationAssessor	Benign	1.7	L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.17	B;B;B
Vest4		0.36
ClinPred		0.021	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800206; hg19: chr22-46614274; COSMIC: COSV53078520; COSMIC: COSV53078520;