rs768695

Variant names:

• chr4-23797195-G-A
• rs768695
• NM_013261.5:c.2294-1270C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2294-1270C>T		intron_variant	Intron 12 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2294-1270C>T		intron_variant	Intron 12 of 12	1	NM_013261.5	ENSP00000264867.2
PPARGC1A	ENST00000613098.4	c.1913-1270C>T		intron_variant	Intron 11 of 11	1		ENSP00000481498.1
PPARGC1A	ENST00000506055.5	n.*1509-1270C>T		intron_variant	Intron 12 of 12	1		ENSP00000423075.1
PPARGC1A	ENST00000509702.5	n.2334-1270C>T		intron_variant	Intron 12 of 14	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

African (AFR) AF: 0.505 AC: 20902 AN: 41362

American (AMR) AF: 0.480 AC: 7303 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2220 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3553 AN: 5158

South Asian (SAS) AF: 0.611 AC: 2941 AN: 4816

European-Finnish (FIN) AF: 0.458 AC: 4824 AN: 10532

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33436 AN: 67912

Other (OTH) AF: 0.551 AC: 1165 AN: 2114

Alfa AF: 0.509 Hom.: 22897

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
PhyloP100		-1.4
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: rs768695; hg19: chr4-23798818;