rs7672915

Variant names:

• chr4-23854869-C-T
• rs7672915
• NM_013261.5:c.235-23118G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330751.2(PPARGC1A):​c.250-23118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,872 control chromosomes in the GnomAD database, including 20,161 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 (20161 hom., cov: 30)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 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_013261.5	MANE Select	c.235-23118G>A		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.250-23118G>A		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.250-23118G>A		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.235-23118G>A		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-147-23118G>A		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.235-23118G>A		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77250 AN: 151754 Hom.: 20144 Cov.: 30

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.509 AC: 77283 AN: 151872 Hom.: 20161 Cov.: 30 AF XY: 0.512 AC XY: 38027 AN XY: 74234

African (AFR) AF: 0.412 AC: 17052 AN: 41390

American (AMR) AF: 0.449 AC: 6856 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1910 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2353 AN: 5138

South Asian (SAS) AF: 0.426 AC: 2051 AN: 4816

European-Finnish (FIN) AF: 0.685 AC: 7233 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.559 AC: 37990 AN: 67920

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.529 Hom.: 10041

Bravo AF: 0.484

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		0.066
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7672915; hg19: chr4-23856492;