rs7657071

Positions:

• chr4-23894851-C-A
• chr4-23894851-C-T

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-9920G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,966 control chromosomes in the GnomAD database, including 6,661 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 0.29 (6661 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-9920G>T		intron_variant
PPARGC1A	NM_001330752.2	c.19-9920G>T		intron_variant
PPARGC1A	NM_001354825.2	c.70-9920G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.52+4416G>T		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.96+9143G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43875 AN: 151848 Hom.: 6659 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43890 AN: 151966 Hom.: 6661 Cov.: 32 AF XY: 0.280 AC XY: 20823 AN XY: 74268

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.300

Alfa AF: 0.306 Hom.: 10819

Bravo AF: 0.292

Asia WGS AF: 0.183 AC: 639 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7657071; hg19: chr4-23896474;