NM_001330751.2:c.70-9920G>T

Variant names:

• chr4-23894851-C-A
• rs7657071
• NM_001330751.2:c.70-9920G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330751.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_001330751.2		c.70-9920G>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.70-9920G>T		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.70-9920G>T		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000507342.5	TSL:3	n.52+4416G>T		intron	N/A
	PPARGC1A	ENST00000514494.1	TSL:4	n.96+9143G>T		intron	N/A

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

African (AFR) AF: 0.301 AC: 12476 AN: 41462

American (AMR) AF: 0.237 AC: 3608 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1125 AN: 3466

East Asian (EAS) AF: 0.102 AC: 529 AN: 5180

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4828

European-Finnish (FIN) AF: 0.193 AC: 2038 AN: 10540

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21771 AN: 67928

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.308 Hom.: 14294

Bravo AF: 0.292

Asia WGS AF: 0.183 AC: 639 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs7657071; hg19: chr4-23896474;