rs768695

Positions:

• chr4-23797195-G-A
• chr4-23797195-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.2294-1270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,798 control chromosomes in the GnomAD database, including 19,852 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 0.51 (19852 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2294-1270C>T		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2294-1270C>T		intron_variant		1	NM_013261.5	ENSP00000264867	P1
PPARGC1A	ENST00000613098.4	c.1913-1270C>T		intron_variant		1		ENSP00000481498
PPARGC1A	ENST00000506055.5	c.*1509-1270C>T		intron_variant, NMD_transcript_variant		1		ENSP00000423075
PPARGC1A	ENST00000509702.5	n.2334-1270C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76885 AN: 151678 Hom.: 19841 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.507 AC: 76938 AN: 151798 Hom.: 19852 Cov.: 32 AF XY: 0.508 AC XY: 37671 AN XY: 74184

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.551

Alfa AF: 0.507 Hom.: 17604

Bravo AF: 0.511

Asia WGS AF: 0.642 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs768695; hg19: chr4-23798818;