dbSNP rs11734408: PPARGC1A:c.-315T>C (chr4-23880896-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330753.2(PPARGC1A):c.-315T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,138 control chromosomes in the GnomAD database, including 4,371 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 0.21 ( 4370 hom., cov: 32)

Exomes 𝑓: 0.17 ( 1 hom. )

Consequence

PPARGC1A
NM_001330753.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.226

Publications

7 publications found

Variant links:

Genes affected

PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

PPARGC1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330753.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARGC1A	NM_013261.5	MANE Select	c.234+3856T>C	intron	N/A	NP_037393.1
PPARGC1A	NM_001330753.2		c.-315T>C	5_prime_UTR	Exon 1 of 12	NP_001317682.1
PPARGC1A	NM_001330751.2		c.249+3856T>C	intron	N/A	NP_001317680.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARGC1A	ENST00000613098.4	TSL:1	c.-315T>C	5_prime_UTR	Exon 1 of 12	ENSP00000481498.1
PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.234+3856T>C	intron	N/A	ENSP00000264867.2
PPARGC1A	ENST00000506055.5	TSL:1	n.234+3856T>C	intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32595

AN:

152008

Hom.:

4372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0950

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.0314

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.214

AC:

32592

AN:

152126

Hom.:

4370

Cov.:

AF XY:

0.214

AC XY:

15930

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0948

AC:

3937

AN:

41528

American (AMR)

AF:

0.150

AC:

2286

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

706

AN:

3472

East Asian (EAS)

AF:

0.0315

AC:

163

AN:

5172

South Asian (SAS)

AF:

0.171

AC:

826

AN:

4820

European-Finnish (FIN)

AF:

0.362

AC:

3820

AN:

10558

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.296

AC:

20103

AN:

67976

Other (OTH)

AF:

0.201

AC:

426

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1247

2494

3740

4987

6234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

8269

Bravo

AF:

0.188

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.4

(source)

DANN

Benign

0.60

PhyloP100

0.23

PromoterAI

0.076

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over